Cosmetic compositions comprising oridonin and new cosmetic uses

ABSTRACT

The present invention related to cosmetic compositions comprising oridonin and new cosmetic uses. Oridonin is used for fighting the signs of cutaneous aging and for slimming. A composition comprising a combination of oridonin and darutigenol or a derivative thereof, in particular darutoside, is disclosed together with the cosmetic use of such composition.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a national phase entry under 35 U.S.C. §371of International Application No. PCT/IB2010/051651 filed Apr. 15, 2010,published in English, which claims priority from FR0901889 filed Apr.17, 2009, all of which are incorporated herein by reference.

TECHNICAL FIELD

The present invention concerns the cosmetic use of oridonin to fight thecutaneous signs of aging. It also concerns a cosmetic compositioncomprising oridonin and darutigenol or a derivative thereof likedarutoside and its use in cosmetic fields.

The present invention relates to the industries of chemical, cosmeticalor care products for skin and its appendages (like hair, eyelashes,eyebrows, nails, hairs) of mammalians, animals or humans.

BACKGROUND ART

During aging, a progressive decline in the functions of the skin isobserved and gives rise, among other things, to the emergence ofheterogeneity of the skin. Thus, with aging, the skin changes, thisgradually affects its appearance: redness, blemishes, wrinkles,firmness, or smooth.

Skin aging does not result from a single phenomenon but ismultifactorial. Three components may be cited: a genetic component, anenvironmental component and a behavioral component. Alone or incombination, the three components induce, at a variable rate, profoundchanges in the structure and quality of the skin that are frequentlyvisible on the surface of the skin.

Thus, the cosmetic industries are constantly looking for new compoundsable to offer beauty and vitality prolonged skin.

Therefore, the technical problem to resolve was for the inventors of thepresent invention to find compounds able to act remarkably against thedamaging effects of aging skin.

Oridonin is a known molecule corresponding to the following formula:

Oridonin has been tested in vitro, in particular as an active principlefor the treatment of human cancer resistant to Taxol (EP2026780).Oridonin is also disclosed in document JP63141915 as a compound able tostimulate hair growth.

SUMMARY OF THE INVENTION

However, nothing in the prior art suggests the use of oridonin to remedyto esthetical cutaneous disorders linked to aging. Thus, the solution ofthe technical problem is the cosmetic use of oridonin to fight the signsof cutaneous aging. Thanks to the use of oridonin, excellent resultshave been shown by the inventors of the present invention.

The appearance of the skin tissue is greatly improved: the wrinkles andfine lines are blurred, the visible and/or tactile discontinuities arediminished; skin is firmer, more toned and thus more elastic.

The skin is better protected against free radicals. Free radicals areconsidered one of the causes of skin aging, especially as regards theappearance of wrinkles. In particular, free radicals cause direct damageto biological molecules of importance: DNA, proteins, lipids, but alsosecondary lesions by creating toxic byproducts. Oxygen thus generatesdifferent reactive forms including hydrogen peroxide which produces thevery reactive hydroxyl radical. To control these oxidising species, thecell uses antioxidant strategies. Among endogen compounds, reducedglutathione can be found, a tripeptide which is the major actor ofantioxidising defense, fighting against oxygen radicals but also againstperoxides and NO. The inventors of the present invention have thus foundthat oridonin stimulated the synthesis of reduced glutathion and thuswas an excellent detoxifying agent: the skin is detoxified, less dull,it breathes.

The distribution and repartition of the chromophores of the skin is morehomogeneous thanks to the use of oridonin. The apparent rednesses arereduced; complexion is more uniform, smooth and bright.

Chromophores are colored molecules. In the skin, the teen refers tomolecules able to absorb light and whose accumulation is readilyperceived by the eyes.

One the most known cutaneous chromophores is a red chromophore: thehaemoglobin.

The distribution of this chromophore in young skins is very homogeneous,ie with no apparent blood vessels and no localized rednesses. With ageand repeated daily minor stresses, the situation tends to change. Theskin loses its homogeneity due to the impairment of chromophore balance(DEMIRLI et al, 2007). The vascularization becomes more visible atparticular places, frequently those most exposed to the sun, either inthe form of vessels or in the form of diffuse red areas of variableintensity (YAAR, 2006).

In addition to this chromophore, visible to the naked eye, dermalcollagen also has the ability to absorb certain types of photon and thusconstitutes a particular chromophore.

Collagen can now be measured using systems that “see” through the skin.It is known that, with age and stress, collagen, which is a protein ofthe extracellular matrix, is less produced and exhibit greaterdegradation. This weakens the supporting network of the skin, once againheterogeneously. This degradation renders the skin thinner andunderlying structures and defects become visible.

The cutaneous heterogeneity of these two chromophores can be monitoredusing recently developed systems such as the SIAscope® and VISTA®(Montcrieff et al, 2002; Demilri et al, 2007; Matts et al, 2007).

Thus, a first object of the invention related to the cosmetic use oforidonin to fight the signs of skin aging. According to the invention,“fight the signs of skin aging” means a treatment against:

-   -   wrinkles, fine lines, visible and/or tactile skin        discontinuities, loss of firmness, elasticity and tone of skin        tissue;    -   oxidative stress and free radicals;    -   altered distribution of chromophores, thus rebalancing the        distributed haemoglobin and collagen in the skin and thereby        reduce in particular skin rednesses.

To this aim, the inventors of the present invention propose to combineoridonin with at least one of the following compound: fatty acids (oilscomprising DHA/EPA, shea butter, PUFAs, LIPEXEL™), moisturizing agents(HYDRAPROTECTOL™, MOIST-24™), humectants (glycerin, glycols andpolyols), plant extracts like blueberry extract, PHYTOTAL™, PHYTEXCELL™,Boswellia Serrata Gum (boswellic acid), Pilewort extract (RanunculusFicaria), saponins, Skeletonema costatum extract, birch sap extract(Betula Alba) (Sève de Bouleau™/Birch Sap™ of SEDERMA, WO 03/024418),Bacopa Monnieri extract (Bacocalmine™ of SEDERMA, WO 99/40897), roseextracts, bisabolol, D-panthenol, madecassoside, centella asiaticaextract, potassium glycyrrhizinate or cafein, seaweed extracts, aminoacids, peptides (MATRIXYL®, MATRIXYL® 3000, DERMAXYL™, RIGIN™, copperpeptides, Biopeptide CL™, Biopeptide EL™, SYNAKE®, ARGIRELINE®), enzymes(VENUCEANE™, KERATOLINE™), coenzymes (ubiquinone Q10, coenzyme A, R) andco-factors (NADH, NAD, SAM), lightening agents (MAP, LUMISKIN™,MELASLOW™), allantoine, farnesol, polyphenols (HELIOGENOL™),anti-inflammatory agents (bisabolol, NDGA, bacosides, esculosides,Kawain), oligo- and polysaccharides, flavonoids, phytosterols, di- andtriterpens, tannins, alpha- et beta-hydroxy acids, fermentation products(BIODERMINE™, OXYLASTIL™, PHOSPHOVITAL™), Dynalift™, Essenskin™,teprenone (Renovage™, Sederma) and derivatives and structural analogues,Tyr-Arg dipeptide and derivatives comprisingN-Acetyl-Tyrosyl-Arginyl-Hexadecyl ester (Calmosensine™, Sederma),Arnica Montana Flower/Cupressus Sempervirens Seed/PolygonatumMultiflorum extracts (Phytotonine™, Sederma), noraporphines such asglaucine, boldine, diacetylboldine.

More particularly, oridonin is combined with at least one compoundstimulating the extracellular matrix selected from:

-   -   Vitamin A and in particular retinoid retinoic acid, retinol,        retinoic acid, retinyl proprionate retinol palmitate,    -   Vitamin B3 and more particularly niacinamide, tocopherol        nicotinate,    -   Vitamin B5, vitamin B6, vitamin B12,    -   Vitamin C, in particular ascorbic acid, ascorbyl acid, glucoside        ascorbyl, tetrapalmitate ascorbyl, magnesium and sodium ascorbyl        phosphate,    -   Vitamins E, F, H, K, PP,    -   Metalloproteinase inhibitor, TIMP activator,    -   DHEA, precursors and derivatives,    -   Amino acids, such arginine, ornithine, hydroxyproline,        hydroxyproline dipalmitate,    -   Palmitoylglycine, hydroxylysine, methionine and derivatives,    -   Peptides such commercially known under the names: MATRIXYL®,        MATRIXYL® 3000, DERMAXYL™, RIGIN™, copper peptides, Biopeptide        CL™, Carnosine, Biopeptide EL™, SYNAKE™, ARGIRELINE™,    -   Allantoin, farnesol,    -   CAPILECTINE™, ANCRINE™, PROCAPYL™, CAPIGEN™, CAPISLOW™, biotine,        Minoxidil®,    -   Adenosine,    -   Lactic acid, glycolic acid, glucosamine, acetylglucosamine,        madecassic acid, asiaticoside and asiatic acids, ellagic acid,        salicylic acid, stigmasterol, sitosterol, campesterol and        brassicasterol, teprenone, Genistein, equol, hexamidine,        panthenol, dimethylaminoethanol (DMAE),    -   Oils comprising DHA/EPA, shea butter, glycerin,    -   Darutigenol and derivatives, and more particularly darutoside.

Preferably, oridinin is combined with darutigenol or combined withdarutoside.

Darutigenol has the following formula:

while darutoside corresponds to a sugar derivative form of darutigenol,having the following formula:

Thus, according to a second object, the invention relates to acomposition comprising, in a physiologically acceptable medium, aneffective amount of oridonin and darutigenol or a derivative ofdarutigenol, more particularly darutoside, as active agents.

More particularly, the invention relates to a composition comprising, ina physiologically acceptable medium, an effective amount of oridonin anddarutoside.

Within the scope of the present invention, oridonin, darutigenol anddarutoside can be obtained from any supply source, especially by meansof hemi chemical synthesis, chemical synthesis, enzymatic, by one of themany methodologies of biotechnology, by plant extraction or by any othermeans used to obtain it at reasonable cost in the end-product to be usedindustrially.

According to an embodiment, the extraction is vegetal and oridonin isextracted from Rabdosia rubescens, meanwhile darutigenol and darutosideare extracted from Siegesbeckia orientalis. Siegesbeckia orientalis, aplant also known as “holy herb” or “St. Paul's wort”. Native to India,the plant has spread to various tropical countries including Madagascar,where it is used by the locals as a medicinal plant with a soothing andcicatrizing effect (BOITEAU, 1993).

The plant extraction can be made by the usual techniques, for example byphenolic extraction, using any part of the plant as the flower, seed,fruit, root, tuber, leaf, pericarp. The extraction solvents can beselected from water, propylen glycol, butylen glycol, glycerin, PEG-6Caprylic/capric glycerides, polyethylene glycol, methylic and/or ethylicethers of diglycols, cyclic polyols, ethoxylated or propoxylateddiglycols, alcohols (methanol, ethanol, propanol, butanol), or a mixtureof these solvents. Furthermore, it is possible to produce extracts ofthe present invention by other methods such as, for example, maceration,simple decoction, leaching, extraction under reflux, supercritical CO₂extraction, the extraction with ultrasound or microwaves or finallyusing counter-current techniques, this list being not limited.

The molecule of darutoside can be found under the trade nameDarutigenol™.

The mixtures oridonin/darutigenol or oridonin/darutoside according tothe invention provides, through a synergistic effect, an enhancedcosmetic activity as shown by the in vitro and in vivo results that aregiven thereafter.

Thus, the present invention also relates to the cosmetic use of acomposition comprising oridonin and darutigenol, or the use of acomposition comprising oridonin and darutoside, said composition beingintended to fight the signs of skin aging, including for example:

-   -   wrinkles, fine lines, visible and/or tactile discontinuities of        the skin, loss of firmness, elasticity and tone of the skin        tissues induced inter alia by oxidative stress and free        radicals;    -   the alteration of the distribution of chromophores, thus        rebalancing the distribution of haemoglobin and collagen in the        skin.

Oridonin combined to darutigenol or darutoside also helps reduce age ormelanin spots and reduce or eliminate the cutaneous rednesses.

According to the present invention, oridonin or a combination oforidonin and darutigenol or a combination of oridonin and darutoside, iscombined with a suitable excipient, that is to say a physiologicallyacceptable medium. “Physiological medium” means according to the presentinvention, without limitation, an aqueous or alcoholic, a water-in-oil,an oil-in-water microemulsion, an aqueous gel, an anhydrous gel, aserum, a dispersion of vesicles.

“Physiologically acceptable” means that the compositions or compoundsdescribed are suitable for use in contact with mucous membranes, nails,scalp, hair, hairs and skin of mammals and particularly human withoutrisk of toxicity, of incompatibility, instability, allergic response,and others.

The amount of oridonin in a composition is ranging from 0.00001% to 50%,preferably 0.0001% to 10%, more preferably 0.001% to 3% by weight to thetotal weight of the composition.

The amount of darutigenol or derivative thereof (in particulardarutoside) is ranging from 0.00001% to 80%, preferably 0.001% to 50%,more preferably 0.01% to 3% by weight to the total weight of thecomposition.

Preferably, the weight ratio of oridonin/darutigenol or derivativethereof (in particular darutoside) is ranging from 1:1000 to 10:1,preferably 1:1000 and 1:1, more preferably 1:100 and 1:1.

It is particularly interesting to associate oridonin with sunscreens ororganic or inorganic UV filters. The organic UV filters particularlypreferred are chosen from the following compounds: EthylhexylSalicylate, Butyl methoxydibenzoylmethane, Ethylhexyl Methoxycinnamate,Octocrylene, phenylbenzimidazole sulfonic acid, TerephthalylideneDicamphor sulfonic acid, benzophenone-3, Benzophenone-4,Benzophenone-5,4 methylbenzylidene camphor, Benzimidazilate,Anisotriazine, Ethylhexyl triazone, diethylhexyl Butamido triazone,Methylene bis-Benzotriazolyl Tetramethylbutylphenol, Drometrizoletrisiloxane, and mixtures thereof. The inorganic UV filters particularlypreferred are nanopigments of titanium oxide (amorphous or crystallizedin rutile and/or anatase forms), iron, zinc, zirconium or cerium.Coating agents are moreover alumina and/or aluminum stearate. Apreferred TiO₂/MnO₂ sunscreen is Optisol™ proposed by Oxonica.

The terms “adjuvant”, “additives” and “optional compound” are used as asynonym for “additional ingredients”. “The active substances” aresynonyms of “active ingredients”.

All percentages and ratios used in this application are by weight oftotal composition and all measurements are made at 25° C. unless it isspecified otherwise.

In addition, the inventors have also found slimming effects, includingreducing the expansion and/or preventing the installation of adiposetissue through the cosmetic use of oridonin.

Thus, according to another aspect of the invention, it has beendiscovered that the oridonin possesses remarkable properties as aslimming agent.

The inventors recommend to combine oridonin with different compoundsknown for their slimming action such as Centella asiatica, asiaticosideand asiatic acid, caffein, thein and methyl xanthines, theophylline,theobromine, forskolin, esculin and esculoside, ACE inhibitors, Val-Trp,Captopryl™, inhibitors of Neuropeptide Y, enkephalin, gingko biloba,yam, Dioscorea extracts, rutin extract, yerba mate extract, guaranaextract, oligosaccharides, exopolysaccharides, alcohol, carnitine, ivyextract, fucus extract, algae extract, extract of Peumus Boldus,palmitoylcamitine, carnosine, taurine, cyclic AMP, elderberry extract,Phtyosonic™, Vexel™, Coaxel™, Pleurimincyl™, Lipocare™, Unislim™,Bodyfit™, noraporphines and their derivatives.

Furthermore, oridonin can be combined with one or more other activeingredients in order advantageously to obtain a cosmetic product havingan even wider range of properties. Thus, the composition of the presentinvention may contain at least one additional active agent chosen inparticular among anti-aging, whitening, moisturizing, slimming,anti-acne, anti-inflammatory and anti-hair loss agents, as describedbelow in the detailed description of the invention.

According to an embodiment, it is proposed to combine the composition oforidonin and darutigenol or the composition of oridonin and darutosidewith the ingredient(s) sold by Sederma VENUCEANE™ (an anti ageing agentcontaining thermus thermophilus ferment) and/or OLIGOCEANE (arevitalizer agent containing mineral salts, trace elements inparticular, extracted from marine sediments and oyster shells).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts change in dermal collagen density of the necklinedetermined using echography (Echography+image analysis, n=25). Dataindicate that with the cream according to the invention, there was amarked increase in the most echogenic zones reflecting an increase inthe density of dermal fibers such as collagen. The increase, which wasnoteworthy and significant as of the first month of application,increased further after 2 months, reaching 17.5% (p<0.01). In parallel,the control site showed little change. * p<0.05 versus TO/** p<0.01versus TO/$ p<0.05 versus control/$$ p<0.01 versus control.

FIG. 2 depicts collagen heterogeneity, and the correlation between thechange in standard deviation and change in theoretical age with regardto the data presented in Table 15. The results obtained were correlatedwith published results (MATTS et al., 2005) in order to express the pre-vs. post-change in the heterogeneity of collagen distribution(equivalent to a standard deviation) as a variation in age.

DETAILED DESCRIPTION

The present invention will be better understood from the followingdescription.

The term “cosmetic composition” or simply “composition” according to thepresent invention, concerns a formulation which may be used for cosmeticor hygiene purposes or as a base for one or more pharmaceuticalingredients. These also include cosmetics, personal care products andpharmaceutical preparations. It is also possible that these formulationsmay be used for two or more purposes at the same time. A medicalanti-dandruff shampoo, for example, has pharmacological properties andis used as a personal care product to obtain healthy hair.

Some compositions from the present invention may also provide additionalbenefits including stability, lack of significant irritation of the skin(unacceptable to the consumer), anti-inflammatory activity and goodaesthetics.

I. ADDITIVES

The compositions of the invention may include various additional otheringredients, conventional or not. Of course, a decision to include anadditional ingredient and the choice of a specific active ingredient andof additional ingredients depends on the specific application andproduct formulation. The line of demarcation between an “active”ingredient and an “additional” ingredient is therefore artificial anddepends on the specific application and product type. A substance thatis an “active” ingredient in one application or product may be a“functional” ingredient in another, and vice versa.

The compositions of the invention may include one or more additionalingredients, various, conventional or not, which will provide somebenefit to the object of the composition. Such additional ingredientsmay include one or more substances such as, without limitations,cleaning agents, hair conditioning agents, skin conditioning agents,hair styling agents, antidandruff agents, hair growth promoters,perfumes, sunscreen and/or sunblock compounds, pigments, moisturizers,film formers, hair colors, make-up agents, detergents, pharmaceuticals,thickening agents, emulsifiers, humectants, emollients, antisepticagents, deodorant actives, surfactants and propellants.

In a preferred embodiment, where the composition is to be in contactwith human keratinous tissue, the additional ingredients should besuitable for application to keratinous tissue, that is, whenincorporated into the composition they are suitable for use in contactwith human keratinous tissue (hair, nails, skin, lips) without unduetoxicity, incompatibility, instability, allergic response, and the likewithin the scope of sound medical judgment.

The CTFA Cosmetic Ingredient Handbook, Tenth Edition (published by theCosmetic, Toiletry, and Fragrance Association, Inc., Washington D.C.)(2004) describes a non limited wide variety of cosmetic andpharmaceutical ingredients usually used in the skin care industry thatcan be used as additional ingredients in the compositions of the presentinvention. Examples of these ingredient classes include, but are notlimited to: healing agents, skin anti-aging agents, skin moisturizingagents, anti-wrinkle agents, anti-atrophy agents, skin smoothing agents,antibacterial agents, antifungal agents, pesticides anti parasiticagents, antimicrobial agents, anti-inflammatory agents, anti-pruriginousagents, external anesthetic agents, antiviral agents, keratolyticagents, free radicals scavengers, antiseborrheic agents, antidandruffagents, the agents modulating the differentiation, proliferation orpigmentation of the skin and agents accelerating penetration,desquamating agents, depigmenting or propigmenting agents, antiglycationagents, tightening agents, agents stimulating the synthesis of dermal orepidermal macromolecules and/or preventing their degradation; agentsstimulating the proliferation of fibroblasts and/or keratinocytes orstimulating the differentiation of keratinocytes; muscle relaxants;antipollution and/or anti-free radical agents; slimming agents,anticellulite agents, agents acting on the microcirculation; agentsacting on the energy metabolism of the cells; cleaning agents, hairconditioning agents, hair styling agents, hair growth promoters,sunscreen and/or sunblock compounds, make-up agents, detergents,pharmaceutical drugs, emulsifiers, emollients, antiseptic agents,deodorant actives, dermatologically acceptable carriers, surfactants,abrasives, absorbents, aesthetic components such as fragrances,colorings/colorants, essential oils, skin sensates, cosmeticastringents, anti-acne agents, anti-caking agents, anti foaming agents,antioxidants, binders, biological additives, enzymes, enzymaticinhibitors, enzyme-inducing agents, coenzymes, plant extracts, plantderivatives, plant tissue extracts, plant seed extracts, plant oils,botanicals, botanical extracts, ceramides, peptides, buffering agents,bulking agents, chelating agents, chemical additives, colorants,cosmetic biocides, denaturants, drug astringents, external analgesics,film formers or materials, e.g., polymers, for aiding the film-formingproperties and substantivity of the composition, quaternary derivatives,agents increasing the substantivity, opacifying agents, pH adjusters,propellants, reducing agents, sequestrants, skin bleaching andlightening agents, skin tanning agents, skin-conditioning agents (e.g.,humectants, including miscellaneous and occlusive), skin soothing and/orhealing agents and derivatives, skin treating agents, thickeners, andvitamins and derivatives thereof, peeling agents, moisturizing agents,curative agents, lignans, preservatives, UV absorbers, a cytotoxic, anantineoplastic agent, a fat-soluble active, suspending agents, viscositymodifiers, dyes, nonvolatile solvents, diluents, pearlescent aids, foamboosters, a vaccine, and their mixture.

Said additional ingredient is selected from the group consisting ofsugar amines, glucosamine, D-glucosamine, N-acetyl glucosamine,N-acetyl-D-glucosamine, mannosamine, N-acetyl mannosamine,galactosamine, N-acetyl galactosamine, vitamin B3 and its derivatives,niacinamide, sodium dehydroacetate, dehydroacetic acid and its salts,phytosterols, salicylic acid compounds, hexamidines, dialkanoylhydroxyproline compounds, soy extracts and derivatives, equol,isoflavones, flavonoids, phytantriol, farnesol, geraniol, peptides andtheir derivatives, di-, tri-, tetra-, penta-, and hexapeptides and theirderivatives, lys-thr-thr-lys-ser (SEQ ID NO: 1),palmitoyl-lys-thr-thr-lys-ser (SEQ ID NO:1), carnosine, N-acyl aminoacid compounds, retinoids, retinyl propionate, retinol, retinylpalmitate, retinyl acetate, retinal, retinoic acid, water-solublevitamins, ascorbates, vitamin C, ascorbic acid, ascorbyl glucoside,ascorbyl palmitate, magnesium ascorbyl phosphate, sodium ascorbylphosphate, vitamins their salts and derivatives, provitamins and theirsalts and derivatives, ethyl panthenol, vitamin B, vitamin Bderivatives, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin K,vitamin K derivatives, pantothenic acid and its derivatives, pantothenylethyl ether, panthenol and its derivatives, dexpanthenol, biotin, aminoacids and their salts and derivatives, water soluble amino acids,asparagine, alanine, indole, glutamic acid, water insoluble vitamins,vitamin A, vitamin E, vitamin F, vitamin D, mono-, di-, andtri-terpenoids, beta-ionol, cedrol, and their derivatives, waterinsoluble amino acids, tyrosine, tryptamine, butylated hydroxytoluene,butylated hydroxyanisole, allantoin, tocopherol nicotinate, tocopherol,tocopherol esters, palmitoyl-gly-his-lys, phytosterol, hydroxy acids,glycolic acid, lactic acid, lactobionic acid, keto acids, pyruvic acid,phytic acid, lysophosphatidic acid, stilbenes, cinnamates, resveratrol,kinetin, zeatin, dimethylaminoethanol, natural peptides, soy peptides,salts of sugar acids, Mn gluconate, Zn gluconate, particulate materials,pigment materials, natural colors, piroctone olamine,3,4,4′-trichlorocarbanilide, triclocarban, zinc pyrithione,hydroquinone, kojic acid, ascorbic acid, magnesium ascorbyl phosphate,ascorbyl glucoside, pyridoxine, aloe vera, terpene alcohols, allantoin,bisabolol, dipotassium glycyrrhizinate, glycerol acid, sorbitol acid,pentaerythritol acid, pyrrolidone acid and its salts, dihydroxyacetone,erythrulose, glyceraldehyde, tartaraldehyde, clove oil, menthol,camphor, eucalyptus oil, eugenol, menthyl lactate, witch hazeldistillate, eicosene and vinyl pyrrolidone copolymers, iodopropylbutylcarbamate, a polysaccharide, an essential fatty acid, salicylate,glycyrrhetinic acid, carotenoïdes, ceramides and pseudo-ceramides, alipid complex, oils in general of natural origin such shea butter,apricot oil, onagre oil, prunus oil, palm oil, monoi oil, HEPES;procysteine; O-octanoyl-6-D-maltose; the disodium salt ofmethylglycinediacetic acid, steroids such as diosgenin and derivativesof DHEA; DHEA or dehydroepiandrosterone and/or a precursor or chemicalor biological derivative, N-ethyloxycarbonyl-4-para-aminophenol,bilberry extracts; phytohormones; extracts of the yeast Saccharomycescerevisiae; extracts of algae; extracts of soyabean, lupin, maize and/orpea; alverine and its salts, in particular alverine citrate, extract ofbutcher's broom and of horse chestnut, and mixtures thereof, ametalloproteinase inhibitor.

Further skin care and hair care active ingredients that are particularlyuseful in combination with the tri/tetrapeptide mixture can be found inSEDERMA commercial literature and on the website www.sederma.fr.(herewith incorporated in its entirety).

In any embodiment of the present invention, however, the additionalingredients useful herein can be categorized by the benefit they provideor by their postulated mode of action. However, it is to be understoodthat the additional ingredients useful herein can in some instancesprovide more than one benefit or operate via more than one mode ofaction. Therefore, classifications herein are made for the sake ofconvenience and are not intended to limit the additional ingredients tothat particular application or applications listed.

1) Sugar Amines (Amino Sugars)

The compositions of the present invention can comprise a sugar amine,which is also known as amino sugar. Sugar amine compounds useful in thepresent invention can include those described in PCT Publication WO02/076423 and U.S. Pat. No. 6,159,485.

In one embodiment, the composition comprises from about 0.01% to about15%, more preferably from about 0.1% to about 10%, and even morepreferably from about 0.5% to about 5% by weight of the composition, ofsugar amine.

Sugar amines can be synthetic or natural in origin and can be used aspure compounds or mixtures of compounds (e.g., extracts from naturalsources or mixtures of synthetic materials). For example, glucosamine isgenerally found in many shellfish and can also be derived from fungalsources. As used herein, “sugar amine” includes isomers and tautomers ofsuch and its salts (e.g., HCl salt) and is commercially available fromSigma Chemical Co.

Examples of sugar amines that are useful herein include glucosamine,N-acetyl glucosamine, mannosamine, N-acetyl mannosamine, galactosamine,N-acetyl galactosamine, their isomers (e.g., stereoisomers), and theirsalts (e.g., HCl salt). Preferred for use herein are glucosamine,particularly D-glucosamine and N-acetyl glucosamine, particularlyN-acetyl-D-glucosamine.

2) DHEA

The composition of the present invention may comprise DHEA ordehydroepiandrosterone and/or a precursor or biological or chemicalderivative.

The term “DHEA precursor” concerns biological precursors of said DHEAwhich are likely to transform in DHEA during metabolism, as well as itschemical precursors which are likely to transform in DHEA by exogenchemical reaction. As non limitating examples of biological precursors,A5-pregnenolone, 17ahydroxy pregnenolone and 17ahydroxy pregnenolonesulfate can be cited. Also, as non limitating examples of chemicalprecursors, the sapogenins or their derivatives, such as diosgenine (orspriost-5-en-3-beta-ol), hecogenin, hecogenin acetate, smilagenine andsarsasapogenine, as well as the natural extracts containing them, inparticular fenugrec and Disocorees extracts such as the wild ignameroots or Wild Yam, can be cited.

The term “DHEA derivatives” comprises its chemical derivatives as wellas its biological derivatives. As biological derivatives,A5-androstene-3,7-diol and A4-androstene-3,17-dione can be cited. DHEAsalts, in particular hydrosoluble salts, like DHEA sulfate, can be citedas non limitating examples of chemical derivatives. Esters, suchhydroxcarboxylic acid or DHEA esters disclosed for example in U.S. Pat.No. 5,736,537, or other esters such DHEA salicilate, acetate, valerate(or nheptanoate) and enanthate can also be cited. Derivatives of DHEA(DHEA carbamates, DHEA 2-hydroxy malonate, DHEA aminoacid esters)disclosed in FR 00/03846 in the name of the Applicant can be cited. Thislist is obviously not exhaustive.

3) Metalloproteinase Inhibitors

The term “metalloproteinase inhibitor” relates to all molecule and/orplant or bacterial extract having a inhibitory activity on at least oneof the metalloproteinases expressed or synthetized by or in the skin.The article of Y. HEROUY and al., European Journal of Dermatology, n 3,vol. 10, Avril-Mai 2000 discloses metalloproteinases (pp. 173-180). Thefamily of the metalloproteinases is formed of several well-definedgroups on the basis of their resemblance regarding structure andsubstract specificity (Woessner J. F., Faseb Journal, vol. 5, 1991,2145). Among these groups, there are collagenases able to degradefibrillar collagens (MMP-1 or interstitial collagenase, MMP-8 orneutrophil collagenase, MMP-13 or collagenase 3, MMP-18 or collagenase4), gelatinases degrading type IV collagen or other denatured collagenform (MMP-2 or A gelatinase (72 kDa), MMP-9 or B gelatinase (92 kDa)),stromelysines (MMP-3 or stromelysine 1, MMP-10 or stromelysine 2, MMP-11or stromelysine 3) whose broad spectrum of activity targets proteins ofthe extracellular matrix such as glycoproteins (fibronectine, laminine),proteoglycannes etc., matrilysine (MMP-7), metalloelastase (MMP-12) oralso ou encore les membrane metalloproteinases (MMP-14, MMP-15, MMP-16et MMP-17). Metalloproteinases (MMPs) are proteases that use a metal,mostly zinc coordinated to 3 cystein residues and to a methionine intheir active site and that degrade macromolecular components of theextracellulare matrix and of basal layers at neutral pH (collagen,elastin, etc. . . . ). This group of enzymes is inactivated by metalchelators.

The principal activity regulators of MMPs are the tissue inhibitors ofmetalloproteinases or TIMPs such TIMP-1, TIMP-2, TIMP-3 and TIMP-4(Woessner J. F., Faseb Journal, 1991). Furthermore, the MMPs expressionis also regulated by growth factors, cytokins, oncogens products (ras,jun), or also matrice constituants.

The term “metalloproteinase inhibitors>> according to the presentinvention means all molecule able to reduce the MMPs activity regardingthe gene expression (transcription and translation) or regarding theactivation of the zymogene form of MMPs, or else regarding the localcontrol of active forms.

Furthermore, the metalloproteinase inhibitors according to the presentinvention can also be MMP-1 inhibitors of natural or synthetic origin.The terms “natural origin” or “synthetic origin” mean both ametalloproteinase inhibitor at a pure state or in solution at differentconcentrations, but natural inhibitors are obtained from differentextraction methods of a natural origin term element (for example thelycopene) whereas the inhibitors of synthetical origin are all obtainedvia chemical synthesis.

4) Vitamin B3 Compounds

The compositions of the present invention can include a vitamin B3compound. Vitamin B3 compounds are particularly useful for regulatingskin conditions, as described in U.S. Pat. No. 5,939,082. In oneembodiment, the composition comprises from about 0.001% to about 50%,more preferably from about 0.01% to about 20%, even more preferably fromabout 0.05% to about 10%, and still more preferably from about 0.1% toabout 7%, even more preferably from about 0.5% to about 5%, by weight ofthe composition, of the vitamin B3 compound.

As used herein, “vitamin B3 compound” means a compound having theformula:

wherein R is —CONH2 (i.e., niacinamide), —COOH (i.e., nicotinic acid) or—CH2OH (i.e., nicotinyl alcohol); derivatives thereof; and salts of anyof the foregoing.

Exemplary derivatives of the foregoing vitamin B3 compounds includenicotinic acid esters, including non-vasodilating esters of nicotinicacid (e.g, tocopherol nicotinate, myristyl nicotinate), nicotinyl aminoacids, nicotinyl alcohol esters of carboxylic acids, nicotinic acidN-oxide and niacinamide N-oxide.

Suitable esters of nicotinic acid include nicotinic acid esters ofC1-C22, preferably C1-C16, more preferably C1-C6 alcohols.Non-vasodilating esters of nicotinic acid include tocopherol nicotinateand inositol hexanicotinate; tocopherol nicotinate is preferred.

Other derivatives of the vitamin B3 compound are derivatives ofniacinamide resulting from substitution of one or more of the amidegroup hydrogens. Specific examples of such derivatives includenicotinuric acid (C8H8N2O3) and nicotinyl hydroxamic acid (C6H6N2O2).

Exemplary nicotinyl alcohol esters include nicotinyl alcohol esters ofthe carboxylic acids salicylic acid, acetic acid, glycolic acid,palmitic acid and the like. Other non-limiting examples of vitamin B3compounds useful herein are 2-chloronicotinamide, 6-aminonicotinamide,6-methylnicotinamide, n-methyl-nicotinamide, n,n-diethylnicotinamide,n-(hydroxymethyl)-nicotinamide, quinolinic acid imide, nicotinanilide,n-benzylnicotinamide, n-ethylnicotinamide, nifenazone, nicotinaldehyde,isonicotinic acid, methyl isonicotinic acid, thionicotinamide,nialamide, 1-(3-pyridylmethyl)urea, 2-mercaptonicotinic acid, nicomol,and niaprazine.

Examples of the above vitamin B3 compounds are well known in the art andare commercially available from a number of sources, e.g., the SigmaChemical Company (St. Louis, Mo.); ICN Biomedicals, Inc. (Irvin, Calif.)and Aldrich Chemical Company (Milwaukee, Wis.).

One or more vitamin B3 compounds may be used herein. Preferred vitaminB3 compounds are niacinamide and tocopherol nicotinate. Niacinamide ismore preferred.

When used, salts, derivatives, and salt derivatives of niacinamide arepreferably those having substantially the same efficacy as niacinamide.

Salts of the vitamin B3 compound are also useful herein. Nonlimitingexamples of salts of the vitamin B3 compound useful herein includeorganic or inorganic salts, such as inorganic salts with anionicinorganic species (e.g., chloride, bromide, iodide, carbonate,preferably chloride), and organic carboxylic acid salts (includingmono-, di- and tri-C1-C18 carboxylic acid salts, e.g., acetate,salicylate, glycolate, lactate, malate, citrate, preferablymonocarboxylic acid salts such as acetate). These and other salts of thevitamin B3 compound can be readily prepared by the skilled artisan (“TheReaction of L-Ascorbic and D-Iosascorbic Acid with Nicotinic Acid andIts Amide”, J. Organic Chemistry, Vol. 14, 22-26 (1949)).

The vitamin B3 compound may be included as the substantially purematerial, or as an extract obtained by suitable physical and/or chemicalisolation from natural (e.g., plant) sources. The vitamin B3 compound ispreferably substantially pure, more preferably essentially pure.

5) Dehydro Acetic Acid (DHA)

The composition of this invention can include dehydroacetic acid, havingthe structure:

or pharmaceutically acceptable salts, derivatives or tautomers thereof.The technical name for dehydroacetic acid is3-Acetyl-6-methyl-2H-pyran-2,4(3H)-dione and can be commerciallypurchased from Lonza.

Pharmaceutically acceptable salts include alkali metal salts, such assodium and potassium; alkaline earth metal salts, such as calcium andmagnesium; non-toxic heavy metal salts; ammonium salts; andtrialkylammonium salts, such astrimethylammonium and triethylammonium.Sodium, potassium, and ammonium salts of dehydroacetic acid arepreferred. Highly preferred is sodium dehydroacetate which can bepurchased from Tri-K, as Tristat SDHA. Derivatives of dehydroacetic acidinclude, but are not limited to, any compounds wherein the CH3 groupsare individually or in combination replaced by amides, esters, aminogroups, alkyls, and alcohol esters. Tautomers of dehydroacetic acid canbe described as having the chemical formula C8H8O4 and generally havingthe structure above.

In one embodiment, the compositions of the present invention cancomprise from about 0.001% to about 25% by weight of the composition,preferably from about 0.01% to about 10%, more preferably from about0.05% to about 5%, and even more preferably from about 0.1% to about 1%,of dehydroacetic acid or pharmaceutically acceptable salts, derivativesor tautomers thereof.

6) Phytosterol

The compositions of the present invention can comprise a phytosterol.For example, one or more phytosterols can be selected from the groupconsisting of β-sitosterol, campesterol, brassicasterol,Δ5-avennasterol, lupenol, α-spinasterol, stigmasterol, theirderivatives, analogs, and combinations thereof. More preferably, thephytosterol is selected from the group consisting of β-sitosterol,campesterol, brassicasterol, stigmasterol, their derivatives, andcombinations thereof. More preferably, the phytosterol is stigmasterol.

Phytosterols can be synthetic or natural in origin and can be used asessentially pure compounds or mixtures of compounds (e.g., extracts fromnatural sources). Phytosterols are generally found in the unsaponifiableportion of vegetable oils and fats and are available as free sterols,acetylated derivatives, sterol esters, ethoxylated or glycosidicderivatives. More preferably, the phytosterols are free sterols. As usedherein, “phytosterol” includes isomers and tautomers of such and iscommercially available from Aldrich Chemical Company, Sigma ChemicalCompany, and Cognis.

In one embodiment, the composition of the present invention comprisesfrom about 0.0001% to about 25%, more preferably from about 0.001% toabout 15%, even more preferably from about 0.01% to about 10%, stillmore preferably from about 0.1% to about 5%, and even more preferablyfrom about 0.2% to about 2% phytosterol, by weight of the composition.

7) Salicylic Acid Compound

The compositions of the present invention may comprise a salicylic acidcompound, its esters, its salts, or combinations thereof. In oneembodiment of the compositions of the present invention, the salicylicacid compound preferably comprises from about 0.0001% to about 25%, morepreferably from about 0.001% to about 15%, even more preferably fromabout 0.01% to about 10%, still more preferably from about 0.1% to about5%, and even more preferably from about 0.2% to about 2%, by weight ofthe composition, of salicylic acid.

8) Hexamidine

The compositions of the present invention can include hexamidinecompounds, its salts, and derivatives. In one embodiment, the hexamidinecomprises from about 0.0001% to about 25%, more preferably from about0.001% to about 10%, more preferably from about 0.01% to about 5%, andeven more preferably from about 0.02% to about 2.5% by weight of thecomposition.

As used herein, hexamidine derivatives include any isomers and tautomersof hexamidine compounds including but not limited to organic acids andmineral acids, for example sulfonic acid, carboxylic acid, etc.Preferably, the hexamidine compounds include hexamidine diisethionate,commercially available as Eleastab® HP100 from LaboratoiresSerobiologiques.

9) Dialkanoyl Hydroxyproline Compounds

The compositions of the present invention can comprise one or moredialkanoyl hydroxyproline compounds and their salts and derivatives.

In one embodiment, the dialkanoyl hydroxyproline compounds preferablycomprise from about 0.01% to about 10%, more preferably from about 0.1%to about 5%, even more preferably from about 0.1% to about 2% by weightof the composition

Suitable derivatives include but are not limited to esters, for examplefatty esters, including, but not limited to tripalmitoyl hydroxyprolineand dipalmityl acetyl hydroxyproline. A particularly useful compound isdipalmitoyl hydroxyproline. As used herein, dipalmitoyl hydroxyprolineincludes any isomers and tautomers of such and is commercially availableunder the tradename Sepilift DPHP® from Seppic, Inc. Further discussionof dipalmitoyl hydroxyproline appears in PCT Publication WO 93/23028.Preferably, the dipalmitoyl hydroxyproline is the triethanolamine saltof dipalmitoyl hydroxyproline.

10) Flavonoids.

The compositions of the present invention can comprise a flavonoidcompound. Flavonoids are broadly disclosed in U.S. Pat. Nos. 5,686,082and 5,686,367. As used herein, “flavonoid” means unsubstituted flavonoïdor substituted flavonoid (i.e. mono-substituted flavonoid, or/anddi-substituted flavonoid, or/and tri-substituted flavonoid). Examples offlavonoids particularly suitable for use in the present invention areone or more flavones, one or more flavanones, one or more isoflavones,one or more coumarins, one or more chromones, one or more dicoumarols,one or more chromanones, one or more chromanols, isomers (e.g.,cis/trans isomers) thereof, and mixtures thereof.

Preferred for use herein are flavones and isoflavones, in particulardaidzein (7,4′-dihydroxy isoflavone), genistein (5,7,4′-trihydroxyisoflavone), equol (7,4′-dihydroxy isoflavan), 5,7-dihydroxy-4′-methoxyisoflavone, soy isoflavones (a mixture extracted from soy) and otherplant sources of such mixtures (e.g., red clover), and mixtures thereof.Also preferred are favanones such as hesperitin, hesperidin, andmixtures thereof.

Flavonoid compounds useful herein are commercially available from anumber of sources, e.g., Indofine Chemical Company, Inc., Steraloids,Inc., and Aldrich Chemical Company, Inc. Suitable flavonoïdes arecommercially available called Sterocare® offered by SEDERMA anddescribed in WO 99/18927.

In one embodiment, the herein described flavonoid compounds comprisefrom about 0.01% to about 20%, more preferably from about 0.1% to about10%, and even more preferably from about 0.5% to about 5%, by weight ofthe composition.

11) N-Acyl Amino Acid Compound

The topical compositions of the present invention can comprise one ormore N-acyl amino acid compounds. The amino acid can be one of any ofthe amino acids known in the art. The N-acyl amino acid compounds of thepresent invention can correspond to the formula:

wherein R can be a hydrogen, alkyl (substituted or unsubstituted,branched or straight chain), or a combination of alkyl and aromaticgroups.

Preferably, the N-acyl amino acid compound is selected from the groupconsisting of N-acyl Phenylalanine, N-acyl Tyrosine, their isomers,their salts, and derivatives thereof. The amino acid can be the D or Lisomer or a mixture thereof

Among the broad class of N-acyl Phenylalanine derivatives, particularlyuseful is N-undecylenoyl-L-phenylalanine commercially available underthe tradename Sepiwhite® from SEPPIC.

In one embodiment, of the present invention, the N-acyl amino acidpreferably comprises from about 0.0001% to about 25%, more preferablyfrom about 0.001% to about 10%, more preferably from about 0.01% toabout 5%, and even more preferably from about 0.02% to about 2.5% byweight of the composition.

12) Retinoid

The compositions of this invention can comprise a retinoid, preferablyin a safe and effective amount such that the resultant composition issafe and effective for regulating keratinous tissue condition,preferably for regulating visible and/or tactile discontinuities inkeratinous tissue (e.g., regulating signs of skin aging). Thecompositions can comprise from about 0.001% to about 10%, morepreferably from about 0.005% to about 2%, even more preferably fromabout 0.01% to about 1%, still more preferably from about 0.01% to about0.5%, by weight of the composition, of the retinoid. The optimumconcentration used in a composition will depend on the specific retinoidselected since their potency can vary considerably.

As used herein, “retinoid” includes all natural and/or synthetic analogsof Vitamin A or retinol-like compounds which possess the biologicalactivity of Vitamin A in the skin as well as the geometric isomers andstereoisomers of these compounds. The retinoid is preferably selectedfrom retinol, retinol esters (e.g., C2-C22 alkyl esters of retinol,including retinyl palmitate, retinyl acetate, retinyl propionate),retinal, and/or retinoic acid (including all-trans retinoic acid and/or13-cis-retinoic acid), or mixtures thereof. More preferably the retinoidis a retinoid other than retinoic acid. These compounds are well knownin the art and are commercially available from a number of sources,e.g., Sigma Chemical Company, and Boerhinger Mannheim. Other retinoidswhich are useful herein are described in U.S. Pat. No. 4,677,120, U.S.Pat. No. 4,885,311, U.S. Pat. No. 5,049,584, U.S. Pat. No. 5,124,356,and Reissue 34,075. Other suitable retinoids can includetocopheryl-retinoate [tocopherol ester of retinoic acid (trans- orcis-), adapalene {6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid},and tazarotene (ethyl6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl]nicotinate). Preferredretinoids include retinol, retinyl palmitate, retinyl acetate, retinylpropionate, retinal and combinations thereof. More preferred is retinylpropionate, used most preferably from about 0.1% to about 0.3%.

The retinoid may be included as the substantially pure material, or asan extract obtained by suitable physical and/or chemical isolation fromnatural (e.g., plant) sources. The retinoid is preferably substantiallypure, more preferably essentially pure.

13) Optional Peptide

The composition of the present invention can comprise an additionalpeptide. Suitable peptides can include, but are not limited to, di-,tri-, tetra-, penta-, and hexa-peptides and derivatives thereof. In oneembodiment, the composition comprises from about 1×10-7% to about 20%,more preferably from about 1×10-6% to about 10%, even more preferablyfrom about 1×10-5% to about 5%, by weight of additional peptide.

As used herein, “peptide” refers to peptides containing ten or feweramino acids and their derivatives, isomers, and complexes with otherspecies such as metal ions (e.g., copper, zinc, manganese, magnesium,and the like). As used herein, peptide refers to both naturallyoccurring and synthesized peptides. Also useful herein are naturallyoccurring and commercially available compositions that contain peptides.

Suitable dipeptides for use herein include but are not limited toCarnosine (beta-Ala-His), Tyr-Arg, Val-Trp (WO 0164178), Asn-Phe,Asp-Phe. Suitable tripeptides for use herein include, but are notlimited to Arg-Lys-Arg (Peptide CK), His-Gly-Gly. Gly-His-Lys,Gly-Gly-His, Gly-His-Gy, Lys-Phe-Lys. Suitable tetrapeptides for useherein include but are not limited to, Peptide E, Arg-Ser-Arg-Lys (SEQID NO: 2), Gly-Gln-Pro-Arg (SEQ ID NO: 3). Suitable pentapeptidesinclude, but are not limited to Lys-Thr-Thr-Lys-Ser (SEQ ID NO: 1).Suitable hexapeptides include but are not limited toVal-Gly-Val-Ala-Pro-Gly (SEQ ID NO: 4) and such as those disclosed in FR2854897 and US 2004/0120918.

Other suitable peptides for use herein include, but are not limited tolipophilic derivatives of peptides, preferably palmitoyl derivatives,and metal complexes of the aforementioned (e.g., copper complex of thetripeptide His-Gly-Gly). Preferred dipeptide derivatives includeN-Palmitoyl-beta-Ala-His, N-Acetyl-Tyr-Arg-hexadecylester (CALMOSENSINE™from SEDERMA, France, WO 9807744, U.S. Pat. No. 6,372,717). Preferredtripeptide derivatives include N-Palmitoyl-Gly-Lys-His, (Pal-GKH fromSEDERMA, France, WO 0040611), a copper derivative of His-Gly-Gly soldcommercially as lamin, from Sigma, lipospondin (N-Elaidoyl-Lys-Phe-Lys)and its analogs of conservative substitution, N-Acetyl-Arg-Lys-Arg-NH2(Peptide CK+), N-Biot-Gly-His-Lys (N-Biot-GHK from SEDERMA, WO0058347)and derivatives thereof. Suitable tetrapeptide derivatives for useherein include, but are not limited to N-palmitoyl-Gly-Gln-Pro-Arg (SEQID NO: 3) (from SEDERMA, France), suitable pentapeptide derivatives foruse herein include, but are not limited toN-Palmitoyl-Lys-Thr-Thr-Lys-Ser (SEQ ID NO: 1) (available as MATRIXYL™from SEDERMA, France, WO 0015188 and U.S. Pat. No. 6,620,419)N-Palmitoyl-Tyr-Gly-Gly-Phe-X with X Met or Leu or mixtures thereof (SEQID NO: 5). Suitable hexapeptide derivatives for use herein include, butare not limited to N-Palmitoyl-Val-Gly-Val-Ala-Pro-Gly (SEQ ED NO: 4)and derivatives thereof.

The preferred compositions commercially available containing atripeptide or a derivative include Biopeptide-CL™ by SEDERMA(WO0143701), Maxilip™ by SEDERMA (WO 0143701), Biobustyl™ by SEDERMA.The compositions commercially available preferred sources oftetrapeptides include RIGIN™ (WO0043417), EYELISS™ (WO03068141),MATRIXYL™ RELOADED, and MATRIXYL 3000™ which contain between 50 and 500ppm of palmitoyl-Gly-Gln-Pro-Arg (SEQ ID NO: 3), and carrier, proposedby SEDERMA, France (US2004/0132667).

14) Ascorbates and Other Vitamins

The compositions of the present invention may comprise one or morevitamins, such as ascorbates (e.g., vitamin C, vitamin C derivatives,ascorbic acid, ascorbyl glucoside, ascorbyl palmitate, magnesiumascorbyl phosphate, sodium ascorbyl phosphate). Such vitamins caninclude, but are not limited to, vitamin B, vitamin B derivatives,vitamin B1 to vitamin B12 and theirs derivatives, vitamin K, vitamin Kderivatives, vitamin H vitamin D, vitamin D derivatives, vitamin E,vitamin E derivatives, and provitamins thereof, such as panthenol andmixtures thereof. The vitamin compounds may be included as thesubstantially pure material, or as an extract obtained by suitablephysical and/or chemical isolation from natural (e.g., plant) sources.In one embodiment, when vitamin compounds are present in thecompositions of the instant invention, the compositions comprise fromabout 0.0001% to about 50%, more preferably from about 0.001% to about10%, still more preferably from about 0.01% to about 8%, and still morepreferably from about 0.1% to about 5%, by weight of the composition, ofthe vitamin compound.

15) Particulate Material

The compositions of the present invention can comprise one or moreparticulate materials. Non limiting examples of particulate materialsuseful in the present invention include colored and uncolored pigments,interference pigments, inorganic powders, organic powders, compositepowders, optical brightener particles, and combinations thereof. Theseparticulates can, for instance, be platelet shaped, spherical, elongatedor needle-shaped, or irregularly shaped, surface coated or uncoated,porous or non-porous, charged or uncharged, and can be added to thecurrent compositions as a powder or as a pre-dispersion. In oneembodiment, particulate materials are present in the composition inlevels of from about 0.01% to about 20%, more preferably from about0.05% to about 10%, still more preferably from about 0.1% to about 5%,by weight of the composition. There are no specific limitations as tothe pigment, colorant or filler powders used in the composition.

Particulate materials useful herein can include, but are not limited to,bismuth oxychloride, sericite, mica, mica treated with barium sulfate orother materials, zeolite, kaolin, silica, boron nitride, lauroyl lysine,nylon, polyethylene, talc, styrene, polypropylene, polystyrene,ethylene/acrylic acid copolymer, aluminum oxide, silicone resin, bariumsulfate, calcium carbonate, cellulose acetate, PTFE, polymethylmethacrylate, starch, modified starches such as aluminum starch octenylsuccinate, silk, glass, and mixtures thereof. Preferred organicpowders/fillers include, but are not limited, to polymeric particleschosen from the methylsilsesquioxane resin microspheres such as, forexample, those sold by Toshiba silicone under the name Tospearl 145A,microspheres of polymethylmethacrylates such as those sold by Seppicunder the name Micropearl M 100, the spherical particles of crosslinkedpolydimethylsiloxanes, especially such as those sold by Dow CorningToray Silicone under the name Trefil E 506C or Trefil E 505C, sphericalparticles of polyamide and more specifically Nylon 12, especially suchas those sold by Atochem under the name Orgasol 2002D Nat C05,polystyrene microspheres such as for example those sold by DynoParticles under the name Dynospheres, ethylene acrylate copolymer soldby Kobo under the name FloBead EA209, PTFE, polypropylene, aluminumstarch ocetenylsuccinate such as those sold by National Starch under thename Dry Flo, microspheres of polyethylene such as those sold byEquistar under the name of Microthene FN510-00, silicone resin,polymethylsilsesquioxane silicone polymer, platelet shaped powder madefrom L-lauroyl lysine, and mixtures thereof.

Also useful herein are interference pigments. The most common examplesof interference pigments are micas layered with about 50-300 nm films ofTiO2, Fe2O3, silica, tin oxide, and/or Cr2O3. Useful interferencepigments are available commercially from a wide variety of suppliers,for example, Rona (Timiron™ and Dichrona™), Presperse (Flonac™),Englehard (Duochrome™), Kobo (SK-45-R and SK-45-G), BASF (Sicopearls)and Eckart (e.g. Prestige Silk Red).

Other pigments useful in the present invention can provide colorprimarily through selective absorption of specific wavelengths ofvisible light, and include inorganic pigments, organic pigments andcombinations thereof. Examples of such useful inorganic pigments includeiron oxides, ferric ammonium ferrocyanide, manganese violet, ultramarineblue, and Chrome oxide. Organic pigments can include natural colorantsand synthetic monomeric and polymeric colorants. An example isphthalocyanine blue and green pigment. Also useful are lakes, primaryFD&C or D&C lakes and blends thereof. Also useful are encapsulatedsoluble or insoluble dyes and other colorants. Inorganic white oruncolored pigments useful in the present invention, for example TiO2,ZnO, or ZrO2, are commercially available from a number of sources. Oneexample of a suitable particulate material contains the materialavailable from U.S. Cosmetics (TRONOX TiO2 series, SAT-T CR837, a rutileTiO2).

The pigments/powders of the current invention can be surface treated toprovide added stability of color and/or for ease of formulation.Non-limiting examples of suitable coating materials include silicones,lecithin, amino acids, metal soaps, polyethylene and collagen. Thesesurface treatments may be hydrophobic or hydrophilic, with hydrophobictreatments being preferred.

16) Sunscreen Actives

The compositions of the subject invention may optionally contain asunscreen active. As used herein, “sunscreen active” includes bothsunscreen agents and physical sunblocks. Suitable sunscreen actives maybe organic or inorganic.

A wide variety of conventional organic or inorganic sunscreen activesare suitable for use herein. In one embodiment, the compositioncomprises from about 0.1% to about 20%, more typically from about 0.5%to about 10% by weight of the composition, of the sun screen active.Exact amounts will vary depending upon the sunscreen chosen and thedesired Sun Protection Factor (SPF).

As examples of organic screening agents which are active in UV-A and/orUV-B, there may be mentioned in particular those designated below bytheir CTFA name:

-   -   para-aminobenzoic acid derivatives: PABA, Ethyl PABA, Ethyl        Dihydroxypropyl PABA, Ethylhexyl Dimethyl PABA sold in        particular under the name “ESCALOL 507” by ISP, Glyceryl PABA,        PEG-25 PABA sold under the name “UVINUL P25” by BASF,    -   salicyclic derivatives: Homosalate sold under the name “EUSOLEX        HMS” by RONA/EM INDUSTRIES, Ethylhexyl Salicylate sold under the        name “NEO HELIOPAN OS” by HAARMANN and REIMER, Dipropyleneglycol        Salicylate sold under the name “DIPSAL” by SCHER, TEA        Salicylate, sold under the name “NEO HELIOPAN TS” by HAARMANN        and REIMER,    -   dibenzoylmethane derivatives: Butyl Methoxydibenzoylmethane sold        in particular under the trademark “PARSOL 1789” by HOFFMANN LA        ROCHE, Isopropyl Dibenzolylmethane,    -   cinnamic derivatives: Ethylhexyl Methoxycinnamate sold in        particular under the trademark “PARSOL MCX” by HOFFMANN LA        ROCHE, Isopropyl Methoxy Cinnamate, Isoamyl Methoxy Cinnamate        sold under the trademark “NEO HELIOPAN E 1000” by HAARMANN and        REIMER, Cinoxate, DEA Methoxycinnamate, Diisopropyl        Methylcinnamate, Glyceryl Ethylhexanoate Dimethoxycinnamate,    -   ββ′-diphenylacrylate derivatives: Octocrylene sold in particular        under the trademark “UVINUL N539” by BASF, Etocrylene, sold in        particular under the trademark “UVINUL N35” by BASF,    -   benzophenone derivatives: Benzophenone-1 sold under the        trademark “UVINUL 400” by BASF, Benzophenone-2 sold under the        trademark “UVINUL D50” by BASF, Benzophenone-3 or Oxybenzone,        sold under the trademark “UVINUL M40” by BASF, Benzophenone-4        sold under the trademark “UVINUL MS40” by BASF, Benzophenone-5,        Benzophenone-6 sold under the trademark “HELISORB 11” by        NORQUAY, Benzophenone-8 sold under the trademark “SPECTRA-SORB        UV-24” by AMERICAN CYANAMID, Benzophenone-9 sold under the        trademark “UVINUL DS-49” by BASF, Benzophenone-12,    -   benzylidene camphor derivatives: 3-Benzylidene Camphor,        4-Methylbenzylidene Camphor sold under the name “EUSOLEX 6300”        by MERCK, Benzylidene Camphor Sulphonic Acid, Camphor        Benzalkonium Methosulphate, Terephthalylidene Dicamphor        Sulphonic Acid, Polyacrylamidomethyl Benzylidene Camphor,    -   phenylbenzimidazole derivatives: Phenylbenzimidazole Sulphonic        Acid sold in particular under the trademark “EUSOLEX 232” by        MERCK, Benzimidazilate sold under the trademark “NEO HELIOPAN        AP” by HAARMANN and REIMER,    -   triazine derivatives: Anisotriazine sold under the trademark        “TINOSORB S” by CIBA GEIGY, Ethylhexyl triazones sold in        particular under the trademark “UVINUL T150” by BASF,        Diethylhexyl Butamido Triazone sold under the trademark “UVASORB        HEB” by SIGMA 3V,    -   phenylbenzotriazole derivatives: Drometrizole Trisiloxane sold        under the name “SILATRIZOLE” by RHODIA CHIMIE,    -   anthranilic derivatives: Menthyl anthranilate sold under the        trademark “NEO HELIOPAN MA” by HAARMANN and REIMER,    -   imidazoline derivatives: Ethylhexyl Dimethoxybenzylidene        Dioxoimidazoline Propionate,    -   benzalmalonate derivatives: Polyorganosiloxane with        benzalmalonate functional groups sold under the trademark        “PARSOL SLX” by HOFFMANN LA ROCHE, and mixtures thereof.    -   others: dihydroxycinnamic acid derivatives (umbelliferone,        methylumbelliferone, methylaceto-umbelliferone);        trihydroxy-cinnamic acid derivatives (esculetin,        methylesculetin, daphnetin, and the glucosides, esculin and        daphnin); hydrocarbons (diphenylbutadiene, stilbene);        dibenzalacetone and benzalacetophenone; naphtholsulfonates        (sodium salts of 2-naphthol-3,6-disulfonic and of        2-naphthol-6,8-disulfonic acids); di-hydroxynaphthoic acid and        its salts; o- and p-hydroxybiphenyldisulfonates; coumarin        derivatives (7-hydroxy, 7-methyl, 3-phenyl); diazoles        (2-acetyl-3-bromoindazole, phenyl benzoxazole, methyl        naphthoxazole, various aryl benzothiazoles); quinine salts        (bisulfate, sulfate, chloride, oleate, and tannate); quinoline        derivatives (8-hydroxyquinoline salts, 2-phenylquinoline); uric        and violuric acids; tannic acid and its derivatives (e.g.,        hexaethylether); (butyl carbotol) (6-propyl piperonyl) ether;        hydroquinone;

The organic UV-screening agents which are more particularly preferredare chosen from the following compounds: Ethylhexyl Salicylate, ButylMethoxydibenzoylmethane, Ethylhexyl Methoxycinnamate, Octocrylene,Phenylbenzimidazole Sulphonic Acid, Terephthalylidene DicamphorSulphonic, Benzophenone-3, Benzophenone-4,Benzophenone-5,4-Methylbenzylidene camphor, Benzimidazilate,Anisotriazine, Ethylhexyl triazone, Diethylhexyl Butamido Triazone,Methylene bis-Benzotriazolyl Tetramethylbutylphenol, DrometrizoleTrisiloxane, and mixtures thereof.

Also preferred are the compositions described in U.S. Pat. No. 6,190,645and in particular, sunscreen agents sold under the trademarkINCROQUAT-UV-283 manufactured by Croda, Inc.

The inorganic screening agents which may be used in the compositionaccording to the invention are in particular nanopigments (mean size ofthe primary particles: generally between 5 nm and 100 nm, preferablybetween 10 nm and 50 nm) of coated or uncoated metal oxides such as forexample nanopigments of titanium oxide (amorphous or crystallized in theform of rutile and/or anatase), iron, zinc, zirconium or cerium oxidesand mixtures thereof. Coating agents are moreover alumina and/oraluminum stearate. Such nanopigments of metal oxides, coated oruncoated, are in particular described in EP-A-0-518,772 andEP-A-0-518,773.

When used herein, the inorganic sunscreens are present in the amount offrom about 0.1% to about 20%, preferably from about 0.5% to about 10%,more preferably from about 1% to about 5%, by weight of the composition.

17) Anti-Cellulite Agents

The compositions of the present invention may also comprise ananti-cellulite agent. Suitable agents may include, but are not limitedto, xanthine compounds (e.g., caffeine, theophylline, theobromine, andaminophylline In one embodiment, when anti-cellulite compounds arepresent in the compositions of the instant invention, the compositionscomprise from about 0.0001% to about 50%, more preferably from about0.001% to about 10%, still more preferably from about 0.01% to about 8%,and still more preferably from about 0.1% to about 5%, by weight of thecomposition, of the anti-cellulite compound.

Especially useful are combinations with the cellulite/slimming agentscalled Vexel™ (FR 2 654 619), Coaxel (FR 2 694 195), Cyclolipase™ (FR 2733 149), Pleurimincyl™ and Lipocare™ (WO 98/43607) and Unislim™ (FR0306063), all offered by SEDERMA.

18) Slimming, Toning or Draining Actives

The compositions can include one or more lipolytic agent selected among:phosphodiesterase inhibitors (e.g., xanthine derivatives), alpha-2blockers compounds capable of blocking alpha-2 receptors at theadipocytes surface, beta-adrenergical agonists and antagonists (e.g.alverine and its organic or inorganic salts such as alverine citrate),agents inhibiting LDL and VLDL receptors synthesis, inhibitors ofenzymes of fatty acid synthesis such as acetylCoA carboxylase, or fattyacid synthetase or cerulenine, compounds stimulating beta receptorsand/or G proteins, glucose transport blockers such as serutine orrutine, neuropeptide Y (NPY) antagonists capable of blocking NPYreceptors at the adipocytes surface, cAMP and its cosmeticallyacceptable derivatives, adenylate cyclase enzyme active agents such asforskolin, agents modifying fat acids transport, lipolytic peptides andlipolytic proteins, like peptides or proteins such as the peptidesderived from the parathyroidal hormone, described in particular in thepatents FR 2788058 and FR 2781231.

Others examples of usable lipolytic agents include botanical and marineextracts.

-   -   among plant extracts, there may more particularly be mentioned        the extract of English ivy (Hedera Helix), of Chinese thorowax        (Bupleurum chinensis), of arnica (Arnica Montana L), of rosemary        (Rosmarinus officinalis N), of marigold (Calendula officinalis),        of sage (Salvia officinalis L), of ginseng (Panax ginseng), of        ginko biloba, of St.-John's-Wort (Hyperycum Perforatum), of        butcher's-broom (Ruscus aculeatus L), of European meadowsweet        (Filipendula ulmaria L), of big-flowered Jarva tea (Orthosiphon        Stamincus Benth), of algae (Fucus Vesiculosus), of birch (Betula        alba), of green tea, of cola nuts (Cola Nipida), of        horse-chestnut, of bamboo, of spadeleaf (Centella asiatica), of        heather, of fucus, of willow, of mouse-ear, extracts of escine,        extracts of cangzhu, extracts of chrysanthellum indicum,        extracts of the plants of the Armeniacea genus, Atractylodis        Platicodon, Sinnomenum, Pharbitidis, Flemingia, extracts of        Coleus such as C. Forskohlii, C. blumei, C. esquirolii, C.        scutellaroides, C. xanthantus and C. Barbatus, such as the        extract of root of Coleus barbatus, extracts of Ballote,        extracts of Guioa, of Davallia, of Terminalia, of Barringtonia,        of Trema, of antirobia, cecropia, argania, dioscoreae such as        Dioscorea opposita or Mexican,    -   as extracted of marine origin: extracts of algae or        phytoplankton such as an extract of Laminaria digitata, diatoms,        rhodysterol. All these extracts can of course to be taken in        mixtures.

The compositions according to the invention can also contain in additionone or more additional active selected among: agents acting on themicrocirculation (vasculoprotectors or vasodilators) such as the naturalflavonoides, ruscogenines, esculosides, escine, nicotinates, heperidinemethyl chalcone, butcher's-broom, essential oils of lavender orrosemary, the extracts of Ammi visnaga; anti-glycation agents such asextracts of Centella asiatica and Siegesbeckia, silicium, amadorine,ergothioneine and its derivatives, hydroxystilbenes and theirderivatives (e.g. resvératrol), vegetable extracts of the family ofEricaceae, in particular bilberry extracts (Vaccinium angustifollium),vitamin C and its derivatives, retionol and its derivatives.

19) Butylated Hydroxytoluene (BHT) and Butylated Hydroxyanisole (BHA)

The topical compositions of the present invention may comprise BHT orBHA.

In one embodiment, BHT and/or BHA comprises from about 0.0001% to about20% by weight of the composition, more preferably from about 0.001% toabout 10%, even more preferably from about 0.01% to about 5%, and stillmore preferably from about 0.1% to about 0.5%.

20) Topical Anesthetics

The compositions of the present invention may also contain a safe andeffective amount of a topical anesthetic. Examples of topical anestheticdrugs include benzocaine, lidocaine, bupivacaine, chlorprocaine,dibucaine, etidocaine, mepivacaine, tetracaine, dyclonine, hexylcaine,procaine, cocaine, ketamine, pramoxine, phenol, and pharmaceuticallyacceptable salts thereof.

21) Desquamation Actives/Keratolytic Actives

A desquamating/keratolytic active may be added to the compositions ofthe present invention. In one embodiment, the composition comprises fromabout 0.01% to about 10%, preferably from about 0.1% to about 5%, morepreferably from about 0.5% to about 2%, by weight of the composition, ofa desquamating/keratolytic active.

Examples of useful keratolytic and/or desquamating agents include urea,salicylic acid and alkyl derivatives thereof, saturated and unsaturatedmonocarboxylic acids, saturated and unsaturated bicarboxylic acids,tricarboxylic acids, alpha hydroxyacids and beta hydroxyacids ofmonocarboxylic acids, alpha hydroxyacids and beta hydroxyacids ofbicarboxylic acids, alpha hydroxyacids and beta hydroxyacids oftricarboxylic acids, ketoacids, alpha ketoacids, beta ketoacids, of thepolycarboxylic acids, of the polyhydroxy monocarboxylic acids, of thepolyhydroxy bicarboxylic acids, of the polyhydroxy tricarboxylic acids.

Illustrative of this group of materials are 2-hydroxyethanoic acid(glycolic acid); 2-hydroxypropanoic acid (lactic acid); 2-methyl2-hydroxypropanoic acid (methyllactic acid); 2-hydroxybutanoic acid;2-hydroxypentanoic acid; 2-hydroxyhexanoic acid; 2-hydroxyheptanoicacid; 2-hydroxyoctanoic acid; 2hydroxynonanoic acid; 2-hydroxydecanoicacid; 2-hydroxyundecanoic acid; 2-hydroxydodecanoic acid(alpha-hydroxylauric acid); 2-hydroxytetradecanoic acid(alpha-hydroxymyristic acid); 2-hydroxyhexadecanoic acid(alpha-hydroxypalmitic acid); 2-hydroxyoctadecanoic acid(alpha-hydroxystearic acid); 2-hydroxyeicosanoic acid(alpha-hydroxyarachidonic acid); 2-phenyl 2-hydroxyethanoic acid(mandelic acid); 2,2-diphenyl 2-hydroxyethanoic acid (benzilic acid);3-phenyl 2-hydroxypropanoic acid (phenyl lactic acid); 2-phenyl 2-methyl2-hydroxyethanoic acid (atrolactic acid); 2-(4′-hydroxyphenyl)2-hydroxyethanoic acid; 2-(4′-chlorophenyl 2-hydroxyethanoic acid;2-(3′-hydroxy-4′-methoxyphenyl) 2-hydroxyethanoic acid;2-(4′-hydroxy-3′-methoxyphenyl) 2-hydroxyethanoic acid;3′-(2-hydroxyphenyl) 2-hydroxypropanoic acid; 3-(4′-hydroxyphenyl)2-hydroxypropanoic acid; and 2-(3′,4′dihydroxyphenyl), and2-hydroxyethanoic acid, 5-n-octanoylsalicylic acid,5-n-dodecanoylsalicylic acid, 5-n-decanoylsalicylic acid,5-n-octylsalicylic acid, 5-n-heptyloxysalicylic acid,4-n-heptyloxysalicylic acid and 2-hydroxy-3-methylbenzoic acid or alkoxyderivatives thereof, such as 2-hydroxy-3-methyoxybenzoic acid.

Preferred keratolytic agents are selected from the group comprisingglycolic acid, tartaric acid, salicylic acid, citric acid, lactic acid,pyruvic acid, gluconic acid, glucuronic acid, malic acid, mandelic acid,oxalic acid, malonic acid, succinic acid, acetic acid, phenol,resorcine, retinoic acid, adapalene, trichloroacetic acid, 5-fluorouracil, azelaic acid. Keratolytic agents are also the salts, esters,possible cis or trans forms, racemic mixtures and/or the relativedextrorotatory or levorotatory forms of the above listed compounds. Suchsubstances can be used singularly or in associations with each other.

Other keratolytic agents suitable for use herein can include enzymaticexfoliant based on a protease called Keratoline™ and offered by Sederma.

One desquamation system that is suitable for use herein comprisessalicylic acid and zwitterionic surfactants and is described in U.S.Pat. No. 5,652,228. Another desquamation system that is suitable for useherein contains sulfhydryl compounds and zwitterionic surfactants and isdescribed in U.S. Pat. No. 5,681,852. Zwitterionic surfactants such asthose described in this referenced patent can also be useful asdesquamatory agents herein, with cetyl betaine being particularlypreferred.

22) Anti-Acne Actives

The compositions of the present invention can comprise one or moreanti-acne actives. Examples of useful anti-acne actives includeresorcinol, sulfur, erythromycin, salicylic acid, benzoyl peroxide,dehydroacetic acid and zinc. Further examples of suitable anti-acneactives are described in U.S. Pat. No. 5,607,980. Especially useful arecombinations with the anti-acne ingredient called Ac.net™ offered bySEDERMA (WO 03/028692 A2).

In one embodiment, when anti-acne compounds are present in thecompositions of the instant invention, the compositions comprise fromabout 0.0001% to about 50%, more preferably from about 0.001% to about10%, still more preferably from about 0.01% to about 8%, and still morepreferably from about 0.1% to about 5%, by weight of the composition, ofthe anti-acne compound.

23) Anti-Wrinkle Actives/Anti-Atrophy Actives

The compositions of the present invention can comprise a one or moreanti-wrinkle actives or anti-atrophy actives. Exemplaryanti-wrinkle/anti-atrophy actives suitable for use in the compositionsof the present invention include sulfur-containing D and L amino acidsand their derivatives and salts, particularly the N-acetyl derivatives,a preferred example of which is N-acetyl-L-cysteine; thiols, e.g. ethanethiol, hydroxy acids (e.g., alpha-hydroxy acids such as lactic acid andglycolic acid or beta-hydroxy acids such as salicylic acid and salicylicacid derivatives such as the octanoyl derivative, lactobionic acid),keto acids (e.g., pyruvic acid), phytic acid, ascorbic acid (vitamin),stilbenes, cinnamates, resveratrol, kinetin, zeatin,dimethylaminoethanol, peptides from natural sources (e.g., soypeptides), and salts of sugar acids (e.g., Mn gluconate, Zn gluconate),lipoic acid; lysophosphatidic acid, skin peel agents (e.g., phenol andthe like), vitamin B3 compounds and retinoids and othervitamin Bcompounds (e.g., thiamine (vitamin B1), pantothenic acid (vitamin B5),riboflavin (vitamin B2), and their derivatives and salts (e.g., HCLsalts or calcium salts). Especially useful are combinations with thewrinkle agents called Dermolectine™ and Sterocare™ offered by SEDERMA(WO99/18927).

In one embodiment, when anti-wrinkle/anti-atrophy compounds are presentin the compositions of the instant invention, the compositions comprisefrom about 0.0001% to about 50%, more preferably from about 0.001% toabout 10%, still more preferably from about 0.01% to about 8%, and stillmore preferably from about 0.1% to about 5%, by weight of thecomposition, of the anti-wrinkle/anti-atrophy compound.

24) Anti-Oxidants/Radical Scavengers

The compositions of the present invention can include ananti-oxidant/radical scavenger. In one embodiment, the compositioncomprises from about 0.01% to about 10%, more preferably from about 0.1%to about 5%, of an anti-oxidant/radical scavenger.

Anti-oxidants/radical scavengers such as ascorbic acid (vitamin C) andits salts, ascorbyl esters of fatty acids, ascorbic acid derivatives(e.g., magnesium ascorbyl phosphate, sodium ascorbyl phosphate, ascorbylsorbate), tocopherol (vitamin E), tocopherol sorbate, tocopherolacetate, other esters of tocopherol, butylated hydroxy benzoic acids andtheir salts, peroxides including hydrogen peroxide, perborate,thioglycolates, persulfate salts,6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (commerciallyavailable under the tradename Trolox®), gallic acid and its alkylesters, especially propyl gallate, uric acid and its salts and alkylesters, amines (e.g., N,N-diethylhydroxylamine, amino-guanidine),nordihydroguaiaretic acid, bioflavonoids, sulfhydryl compounds (e.g.,glutathione), dihydroxy fumaric acid and its salts, lycine pidolate,arginine pilolate, amino acids, silymarin, lysine, 1-methionine,proline, superoxide dismutase, sorbic acids and its salts, lipoic acid,olive extracts, tea extracts, polyphenols such as proanthocyanidine frompine bark, carotenoids, curcumin compounds such as tetrahydrocurcumin,OCTA (L-2-oxo-4-thiazolidine carboxylic acid), glutathione, melanin,rosemary extracts and grape skin/seed extracts may be used. Preferredanti-oxidants/radical scavengers can be selected from esters oftocopherol, more preferably tocopherol acetate and tocopherol sorbate(U.S. Pat. No. 4,847,071)

25) Humectants, Moisturizers and Conditioning Agents

The compositions of the present invention can contain a safe andeffective amount of a conditioning agent selected from, for example,humectants, moisturizers, and skin conditioners. A variety of thesematerials can be employed and in one embodiment can be present at alevel of from about 0.01% to about 20%, more preferably from about 0.1%to about 10%, and still more preferably from about 0.5% to about 7%, byweight of the composition. These materials can include, but are notlimited to, guanidine, urea, glycolic acid, glycolate salts (e.g.ammonium and quaternary alkyl ammonium), salicylic acid, lactic acid,lactate salts (e.g., ammonium and quaternary alkyl ammonium), aloe verain any of its variety of forms (e.g., aloe vera gel), polyhydroxyalcohols such as sorbitol, mannitol, xylitol, erythritol, glycerol,hexanetriol, butanetriol, propylene glycol, butylene glycol, hexyleneglycol and the like, polyethylene glycols, sugars (e.g., melibiose),starches, sugar and starch derivatives (e.g., alkoxylated glucose,fructose, glucosamine), hyaluronic acid, lactamide monoethanolamine,acetamide monoethanolamine, panthenol, allantoin, petroleum and mixturesthereof. Also useful herein are the propoxylated glycerols described inU.S. Pat. No. 4,976,953.

Also useful are various C1-C30 monoesters and polyesters of sugars andrelated materials. These esters are derived from a sugar or polyolmoiety and one or more carboxylic acid moieties.

Preferably, the conditioning agent is selected from urea, guanidine,sucrose polyester, panthenol, dexpanthenol, allantoin, glycerol, andcombinations thereof.

Humectants can be selected from the group consisting of polyhydricalcohols, water soluble alkoxylated nonionic polymers, and mixturesthereof. Polyhydric alcohols useful herein include polyhdroxy alcoholsaforementioned and glycerin, hexylene glycol, ethoxylated glucose,1,2-hexane diol, dipropylene glycol, trehalose, diglycerin, maltitol,maltose, glucose, fructose, sodium chondroitin sulfate, sodiumhyaluronate, sodium adenosine phosphate, sodium lactate, pyrrolidonecarbonate, glucosamine, cyclodextrin, and mixtures thereof. Watersoluble alkoxylated nonionic polymers useful herein include polyethyleneglycols and polypropylene glycols having a molecular weight of up toabout 1000 such as those with CTFA names PEG-200, PEG-400, PEG-600,PEG-1000, and mixtures thereof.

26) Active Oxygen Generation Inhibitors

The compositions of the present invention may also comprise a an activeoxygen generation inhibitor selected from the group comprisingquercetin, rutin, taxifolin, kaempferol, myricetin, curcumin,resveratrol, arecoline, apigenin, wogonin, luteolin, tectorigenin, and amixture thereof.

This active oxygen generation inhibitor may be contained in an amount ofabout 0.001% to about 5%, more preferably in an amount of about 0.01% toabout 3% %, by weight of the composition.

27) Chelators

The compositions of the present invention may also comprise a chelatoror chelating agent. As used herein, “chelator” or “chelating agent”means an active agent capable of removing a metal ion from a system byforming a complex so that the metal ion cannot readily participate in orcatalyze oxygen radical formation. In one embodiment, a chelating agentis added to a composition of the present invention, preferably fromabout 0.00001% to about 10%, more preferably from about 0.001% to about5%, by weight of the composition. Exemplary chelators that are usefulherein include those that are disclosed in U.S. Pat. No. 5,487,884, WO91/16035 and WO 91/16034. Examples of chelating agents includeN-hydroxysuccinimide, EDTA, NTA, deferoxamine, hydroxamic acids andtheir salts, phytic acid, phytate, gluconic acid and its salts,transferrine, lactoferrin; furildioxime and derivatives thereof.

28) Anti-Inflammatory Agents

An anti-inflammatory agent may be added to the compositions of thepresent invention. In one embodiment, an anti-inflammatory agent isadded at a level of from about 0.01% to about 10%, preferably from about0.5% to about 5%, by weight of the composition. The exact amount ofanti-inflammatory agent to be used in the compositions will depend onthe particular anti-inflammatory agent utilized since such agents varywidely in potency

Steroidal anti-inflammatory agents can include, but are not limited to,corticosteroids such as hydrocortisone. In addition, nonsteroidalanti-inflammatory agents can be useful herein. The varieties ofcompounds encompassed by this group are well known to those skilled inthe art. Specific non-steroidal anti-inflammatory agents that can beuseful in the composition of the present invention include, but are notlimited to, oxicams such as piroxicam, salicylates such as aspirin;acetic acid derivatives, such as felbinac, fenamates, such asetofenamate, flufenamic, mefenamic, meclofenamic, acids; propionic acidderivatives, such as ibuprofen, naproxen, pyrazoles, and mixturesthereof. Mixtures of these non-steroidal anti-inflammatory agents mayalso be employed, as well as the dermatologically acceptable salts andesters of these agents.

Finally, so-called “natural” anti-inflammatory agents are useful inmethods of the present invention. Such agents may suitably be obtainedas an extract by suitable physical and/or chemical isolation fromnatural sources (e.g., plants, fungi, by-products of microorganisms) orcan be synthetically prepared. For example, candelilla wax, bisabolol(e.g., alpha bisabolol), aloe vera, plant sterols (e.g., phytosterol),Manjistha (extracted from plants in the genus Rubia, particularly RubiaCordifolia), and Guggal (extracted from plants in the genus Commiphora,particularly Commiphora Mukul), kola extract, chamomile, red cloverextract, Piper methysticum extract (Kava Kava from SEDERMA (FR 2 771 002and WO 99/25369), Bacopa monieri extract (Bacocalmine™ from SEDERMA, WO99/40897) and sea whip extract, may be used. Anti-inflammatory agentsuseful herein include allantoin and compounds of the Licorice (the plantgenus/species Glycyrrhiza glabra) family, including glycyrrhetic acid,glycyrrhizic acid, and derivatives thereof (e.g., salts and esters).Suitable salts of the foregoing compounds include metal and ammoniumsalts. Suitable esters include C2-C24 saturated or unsaturated esters ofthe acids, preferably C10-C24, more preferably C16-C24. Specificexamples of the foregoing include oil soluble licorice extract, theglycyrrhizic and glycyrrhetic acids themselves, monoammoniumglycyrrhizinate, monopotassium glycyrrhizinate, dipotassiumglycyrrhizinate, 1-beta-glycyrrhetic acid, stearyl glycyrrhetinate, and3-stearyloxy-glycyrrhetinic acid, and disodium3-succinyloxy-beta-glycyrrhetinate. Stearyl glycyrrhetinate ispreferred. Additional anti inflammatory agents include diosgenol,saponines, sapogenins, lignanes, triterpenes saponosides and genines.

29) Tanning Actives

The compositions of the present invention can comprise a tanning active.In one embodiment, the composition comprises from about 0.1% to about20%, more preferably from about 2% to about 7%, and even more preferablyfrom about 3% to about 6%, by weight of the composition, of a tanningactive. A preferred tanning active is dihydroxyacetone, which is alsoknown as DHA or 1,3-dihydroxy-2-propanone. Especially useful arecombinations with the tanning agents called Tyr-ol™ and Tyr-excel™offered by SEDERMA and described in Fr 2 702 766 and WO 03/017966respectively.

30) Skin Withening or Lightening Agents

The compositions of the present invention may contain a skin lighteningagent. When used, the compositions preferably contain from about 0.01%to about 10%, more preferably from about 0.02% to about 5%, alsopreferably from about 0.05% to about 2%, by weight of the composition,of a skin lightening agent. Suitable skin lightening agents includethose known in the art, including kojic acid, arbutin, tranexamic acid,ascorbic acid and derivatives thereof (e.g., magnesium ascorbylphosphate or sodium ascorbyl phosphate, ascorbyl glucoside and thelike), and extracts (e.g., mulberry extract, placental extract). Skinlightening agents suitable for use herein also include those describedin WO95/34280, PCT/US95/07432, co-pending U.S. Ser. No. 08/390,152 andPCT/US95/23780. Especially useful are combinations with the skinlightening agents called Melaclear™, Etioline™, Melaslow™ and Lumiskin™offered by SEDERMA and described respectively in FR 2 732 215, WO98/05299, WO 02/15871 and PCT/FR 03/02400. Other skin lighteningmaterials suitable for use herein can include Actiwhite® (Cognis),Emblica® (Rona), Azeloglicina (Sinerga) and Sepiwhite® (Seppic). Apreferred skin lightening agent is ascorbyl glucoside.

31) Antimicrobial, Antibacterial and Antifungal Actives

The compositions of the present invention can comprise one or moreanti-fungal or anti-microbial actives. A safe and effective amount of anantimicrobial or antifungal active can be added to the presentcompositions. In one embodiment, the composition comprises from about0.001% to about 10%, preferably from about 0.01% to about 5%, and morepreferably from about 0.05% to about 2%, by weight of the composition,of an antimicrobial or antifungal active.

Suitable anti-microbial actives include coal tar, sulfur, whitfield'sointment, castellani's paint, aluminum chloride, gentian violet,octopirox (piroctone olamine), 3,4,4′-trichlorocarbanilide (trichlosan),triclocarban, ciclopirox olamine, undecylenic acid and it's metal salts,potassium permanganate, selenium sulphide, sodium thiosulfate, propyleneglycol, oil of bitter orange, urea preparations, griseofulvin,8-Hydroxyquinoline ciloquinol, thiobendazole, thiocarbamates,haloprogin, polyenes, hydroxypyridone, morpholine, benzylamine,allylamines (such as terbinafine), tea tree oil, clove leaf oil,coriander, palmarosa, berberine, thyme red, cinnamon oil, cinnamicaldehyde, citronellic acid, hinokitol, ichthyol pale, Sensiva SC-50,Elestab HP-100, azelaic acid, lyticase, iodopropynyl butylcarbamate(IPBC), isothiazalinones such as octyl isothiazolinone and azoles, andcombinations thereof. Preferred anti-microbials include itraconazole,ketoconazole, selenium sulphide and coal tar. In one embodiment, one ormore anti-fungal or anti-microbial active is combined with ananti-dandruff active selected from polyvalent metal salts of pyrithione.

a) Azoles

Azole anti-microbials include imidazoles such as benzimidazole,benzothiazole, bifonazole, butoconazole nitrate, climbazole,clotrimazole, croconazole, eberconazole, econazole, elubiol,fenticonazole, fluconazole, flutimazole, isoconazole, ketoconazole,lanoconazole, metronidazole, miconazole, neticonazole, omoconazole,oxiconazole nitrate, sertaconazole, sulconazole nitrate, tioconazole,thiazole, and triazoles such as terconazole and itraconazole, andcombinations thereof. When present in the composition, the azoleanti-microbial active is included in an amount from about 0.01% to about5%, preferably from about 0.1% to about 3%, and more preferably fromabout 0.3% to about 2%, by weight of the composition. Especiallypreferred herein are ketoconazole and climbazole.

b) Selenium Sulfide

Selenium sulfide is a particulate anti-dandruff agent suitable for usein the anti-microbial compositions of the present invention, effectiveconcentrations of which range from about 0.1% to about 4%, by weight ofthe composition, preferably from about 0.3% to about 2.5%, morepreferably from about 0.5% to about 1.5

c) Sulfur

Sulfur may also be used as a particulate anti-microbial/anti-dandruffagent in the anti-microbial compositions of the present invention.Effective concentrations of the particulate sulfur are typically fromabout 1% to about 4%, by weight of the composition, preferably fromabout 2% to about 4%.

d) Additional Anti-Microbial Actives

Additional anti-microbial actives of the present invention may includeone or more keratolytic agents such as salicylic acid, extracts ofmelaleuca (tea tree) and charcoal. The present invention may alsocomprise combinations of anti-microbial actives. Such combinations mayinclude octopirox and zinc pyrithione combinations, pine tar and sulfurcombinations, salicylic acid and zinc pyrithione combinations, octopiroxand climbasole combinations, and salicylic acid and octopiroxcombinations, and mixtures thereof.

Preferred examples of actives useful herein include those selected fromthe group consisting of benzoyl peroxide, 3-hydroxy benzoic acid,glycolic acid, lactic acid, 4-hydroxy benzoic acid, 2-hydroxybutanoicacid, 2-hydroxypentanoic acid, 2-hydroxyhexanoic acid, phytic acid,lipoic acid, azelaic acid, arachidonic acid, benzoylperoxide,tetracycline, ibuprofen, naproxen, hydrocortisone, acetominophen,resorcinol, phenoxyethanol, phenoxypropanol, phenoxyisopropanol,2,4,4′-trichloro-2′-hydroxy diphenyl ether, 3,4,4′-trichlorocarbanilide,octopirox, ciclopirox, lidocaine hydrochloride, clotrimazole,miconazole, ketoconazole, neomycin sulfate, and mixtures thereof.

Especially useful are combinations with the ingredient range calledOSMOCIDE™ offered by SEDERMA (WO 97/05856).

32) Thickening Agents (Including Thickeners and Gelling Agents)

The compositions of the present invention can comprise one or morethickening agents. In one embodiment, a thickening agent is present at alevel of from about 0.05% to about 10%, preferably from about 0.1% toabout 5%, and more preferably from about 0.25% to about 4%, by weight ofthe composition. Nonlimiting classes of thickening agents include thoseselected from the following:

a) Carboxylic Acid Polymers

These polymers are crosslinked compounds containing one or more monomersderived from acrylic acid, substituted acrylic acids, and salts andesters of these acrylic acids and the substituted acrylic acids, whereinthe crosslinking agent contains two or more carbon-carbon double bondsand is derived from a polyhydric alcohol. Polymers useful in the presentinvention are more fully described in U.S. Pat. No. 5,087,445, U.S. Pat.No. 4,509,949, U.S. Pat. No. 2,798,053, and in CTFA InternationalCosmetic Ingredient Dictionary, Tenth Edition, 2004. Examples ofcommercially available carboxylic acid polymers useful herein includethe carbomers, which are homopolymers of acrylic acid crosslinked withallyl ethers of sucrose or pentaerythritol. The carbomers are availableas the Carbopol® 900 series from B.F. Goodrich (e.g., Carbopol® 954). Inaddition, other suitable carboxylic acid polymeric agents includeUltrez® 10 (B.F. Goodrich) and copolymers of C10-30 alkyl acrylates withone or more monomers of acrylic acid, methacrylic acid, or one of theirshort chain (i.e., C1-4 alcohol) esters, wherein the crosslinking agentis an allyl ether of sucrose or pentaerythritol. These copolymers areknown as acrylates/C10-C30 alkyl acrylate crosspolymers and arecommercially available as Carbopol® 1342, Carbopol® 1382, Pemulen TR-1,and Pemulen TR-2, from B.F. Goodrich. In other words, examples ofcarboxylic acid polymer thickeners useful herein are those selected fromcarbomers, acrylates/C10-C30 alkyl acrylate crosspolymers, and mixturesthereof.

b) Crosslinked Polyacrylate Polymers

The compositions of the present invention can optionally containcrosslinked polyacrylate polymers useful as thickeners or gelling agentsincluding both cationic and nonionic polymers, with the cationics beinggenerally preferred. Examples of useful crosslinked nonionicpolyacrylate polymers and crosslinked cationic polyacrylate polymers arethose described in U.S. Pat. No. 5,100,660, U.S. Pat. No. 4,849,484,U.S. Pat. No. 4,835,206, U.S. Pat. No. 4,628,078, U.S. Pat. No.4,599,379 and EP228868.

c) Polyacrylamide Polymers

The compositions of the present invention can optionally containpolyacrylamide polymers, especially nonionic polyacrylamide polymersincluding substituted branched or unbranched polymers. Preferred amongthese polyacrylamide polymers is the nonionic polymer given the CTFAdesignation polyacrylamide and isoparaffin and laureth-7, availableunder the Tradename Sepigel 305 from Seppic Corporation.

Other polyacrylamide polymers useful herein include multi-blockcopolymers of acrylamides and substituted acrylamides with acrylic acidsand substituted acrylic acids. Commercially available examples of thesemulti-block copolymers include Hypan SR150H, SS500V, SS500W, SSSA100H,from Lipo Chemicals, Inc.

The compositions may also contain thickening and texturising gels of thetype as exemplified by the product range called Lubrajel® from UnitedGuardian. These gels have moisturizing, viscosifying, stabilizingproperties and may be used in concentration ranges between 1 and 99%,most advantageously between 5 and 15%.

d) Polysaccharides

A wide variety of polysaccharides can be useful herein.“Polysaccharides” refer to gelling agents that contain a backbone ofrepeating sugar (i.e., carbohydrate) units. Nonlimiting examples ofpolysaccharide gelling agents include those selected from the groupconsisting of cellulose, carboxymethyl hydroxyethylcellulose, celluloseacetate propionate carboxylate, hydroxyethylcellulose, hydroxyethylethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose,methyl hydroxyethylcellulose, microcrystalline cellulose, sodiumcellulose sulfate, and mixtures thereof. Also useful herein are thealkyl-substituted celluloses. Preferred among the alkyl hydroxyalkylcellulose ethers is the material given the CTFA designation cetylhydroxyethylcellulose, which is the ether of cetyl alcohol andhydroxyethylcellulose. This material is sold under the tradenameNatrosol® CS Plus from Aqualon Corporation.

Other useful polysaccharides include scleroglucans comprising a linearchain of (1-3) linked glucose units with a (1-6) linked glucose everythree units, a commercially available example of which is Clearogel™CS11 from Michel Mercier Products Inc.

e) Gums

Other thickening and gelling agents useful herein include materialswhich are primarily derived from natural sources. Nonlimiting examplesof these gelling agent gums include acacia, agar, algin, alginic acid,ammonium alginate, amylopectin, calcium alginate, calcium carrageenan,carnitine, carrageenan, dextrin, gelatin, gellan gum, guar gum, guarhydroxypropyltrimonium chloride, hectorite, hyaluronic acid, hydratedsilica, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp,locust bean gum, natto gum, potassium alginate, potassium carrageenan,propylene glycol alginate, sclerotium gum, sodium carboxymethyl dextran,sodium carrageenan, tragacanth gum, xanthan gum, and mixtures thereof.

33) Antiperspirant Actives

Antiperspirant actives may also be included in the compositions of thepresent invention. Suitable antiperspirant actives include astringentmetallic salts, especially the inorganic and organic salts of aluminumzirconium and zinc, as well as mixtures thereof. Particularly preferredare the aluminum containing and/or zirconium-containing materials orsalts, such as aluminum halides, aluminum chlorohydrate, aluminumhydroxyhalides, zirconyl oxyhalides, zirconyl hydroxyhalides, andmixtures thereof. In one embodiment, when antiperspirant actives arepresent in the compositions of the instant invention, the compositionscomprise from about 0.01% to about 50%, more preferably from about 0.1%to about 40%, and still more preferably from about 1% to about 30%, byweight of the composition, of the antiperspirant compound.

34) Detersive Surfactants

The compositions of the present invention can include detersivesurfactant from about 1% to about 90%, more preferably from about 5% toabout 10%. The detersive surfactant component can be included to providecleaning performance to the composition. The detersive surfactantcomponent in turn can comprise anionic detersive surfactant,zwitterionic or amphoteric detersive surfactant, or a combinationthereof. Suitable anionic detersive surfactant components for use in thecomposition herein include those which are known for use in hair care orother personal care cleansing compositions. When included, theconcentration of the anionic surfactant component in the composition canpreferably be sufficient to provide the desired cleaning and latherperformance, and generally can range from about 5% to about 50%,preferably from about 8% to about 30%, more preferably from about 10% toabout 25%, even more preferably from about 12% to about 22%.

Preferred anionic surfactants suitable for use in the compositions arethe alkyl and alkyl ether sulfates. Other suitable anionic detersivesurfactants are the water-soluble salts of organic, sulfuric acidreaction products, alkoyl isethionates, sodium or potassium salts offatty acid amides of methyl tauride, olefin sulfonates, beta-alkyloxyalkane sulfonates.

Preferred anionic detersive surfactants for use in the compositionsinclude ammonium lauryl sulfate, ammonium laureth sulfate, triethylaminelauryl sulfate, triethylamine laureth sulfate, triethanolamine laurylsulfate, triethanolamine laureth sulfate, monoethanolamine laurylsulfate, monoethanolamine laureth sulfate, diethanolamine laurylsulfate, diethanolamine laureth sulfate, lauric monoglyceride sodiumsulfate, sodium lauryl sulfate, sodium laureth sulfate, potassium laurylsulfate, potassium laureth sulfate, sodium lauryl sarcosinate, sodiumlauroyl sarcosinate, lauryl sarcosine, cocoyl sarcosine, ammonium cocoylsulfate, ammonium lauroyl sulfate, sodium cocoyl sulfate, sodium lauroylsulfate, potassium cocoyl sulfate, potassium lauryl sulfate,triethanolamine lauryl sulfate, triethanolamine lauryl sulfate,monoethanolamine cocoyl sulfate, monoethanolamine lauryl sulfate, sodiumtridecyl benzene sulfonate, sodium dodecyl benzene sulfonate, sodiumcocoyl isethionate and combinations thereof.

Suitable amphoteric or zwitterionic detersive surfactants for use in thecomposition herein include those which are known for use in hair care orother personal care cleansing. Concentration of such amphotericdetersive surfactants preferably ranges from about 0.5% to about 20%,preferably from about 1% to about 10%. Non limiting examples of suitablezwitterionic or amphoteric surfactants are described in U.S. Pat. No.5,104,646 and U.S. Pat. No. 5,106,609.

Amphoteric detersive surfactants include derivatives of aliphaticsecondary and tertiary amines.

The compositions of the present invention may further compriseadditional surfactants for use in combination with the anionic detersivesurfactant component described hereinbefore. Suitable optionalsurfactants include nonionic and cationic surfactants. Any suchsurfactant known in the art for use in hair or personal care productsmay be used, provided that the optional additional surfactant is alsochemically and physically compatible with the essential components ofthe composition, or does not otherwise unduly impair productperformance, aesthetics or stability. The concentration of the optionaladditional surfactants in the composition may vary with the cleansing orlather performance desired, the optional surfactant selected, thedesired product concentration, the presence of other components in thecomposition, and other factors well known in the art.

Non limiting examples of other anionic, zwitterionic, amphoteric oroptional additional surfactants suitable for use in the compositions aredescribed in McCutcheon's, Emulsifiers and Detergents, 1989 Annual,published by M. C. Publishing Co., and U.S. Pat. No. 3,929,678, U.S.Pat. No. 2,658,072, U.S. Pat. No. 2,438,091 and U.S. Pat. No. 2,528,378.

35) Cationic, Anionic and Amphoteric Polymers

The compositions of the present invention can comprise polymers whichmay be homopolymers, copolymers, terpolymers, etc. For convenience indescribing the polymers hereof, monomeric units present in the polymersmay be referred to as the monomers from which they can be derived. Themonomers can be ionic (e.g., anionic, cationic, amphoteric,zwitterionic) or nonionic When included, concentrations of the cationicpolymer in the composition can typically range from about 0.05% to about3%, preferably from about 0.075% to about 2.0%, more preferably fromabout 0.1% to about 1.0

a) Cationic Polymers

Suitable cationic polymers for use in the compositions of the presentinvention contain cationic nitrogen-containing moieties such asquaternary ammonium or cationic protonated amino moieties. Any anioniccounterions can be used in association with the cationic polymers solong as the polymers remain soluble in water, in the composition, or ina coacervate phase of the composition, and so long as the counterionsare physically and chemically compatible with the essential componentsof the composition or do not otherwise unduly impair productperformance, stability or aesthetics. Non limiting examples of suchcounterions include halides (e.g., chloride, fluoride, bromide, iodide),sulfate and methylsulfate. Non limiting examples of such polymers aredescribed in the CTFA.

Non limiting examples of suitable cationic polymers include copolymersof vinyl monomers having cationic protonated amine or quaternaryammonium functionalities with water soluble spacer monomers such asacrylamide, methacrylamide, alkyl and dialkyl acrylamides, alkyl anddialkyl methacrylamides, alkyl acrylate, alkyl methacrylate, vinylcaprolactone or vinyl pyrrolidone.

Examples of cationic monomers include monomers derived from acrylic acidor methacrylic acid, and a quaternarized epihalohydrin product of atrialkylamine having 1 to 5 carbon atoms in the alkyl such as(meth)acryloxypropyltrimethylammonium chloride and(meth)acryloxypropyltriethylammonium bromide; amine derivatives ofmethacrylic acid or amine derivatives of methacrylamide derived frommethacrylic acid or methacrylamide and a dialkylalkanolamine havingC1-C6 alkyl groups such as dimethylaminoethyl (meth)acrylate,diethylaminoethyl (meth)acrylate, dimethylaminopropyl (meth)acrylate, ordimethylaminopropyl (meth)acrylamide

Suitable cationic protonated amino and quaternary ammonium monomers, forinclusion in the cationic polymers of the composition herein, includevinyl compounds substituted with dialkylaminoalkyl acrylate,dialkylaminoalkyl methacrylate, monoalkylaminoalkyl acrylate,monoalkylaminoalkyl methacrylate, trialkyl methacryloxyalkyl ammoniumsalt, trialkyl acryloxyalkyl ammonium salt, diallyl quaternary ammoniumsalts, and vinyl quaternary ammonium monomers having cyclic cationicnitrogen-containing rings such as pyridinium, imidazolium, andquaternized pyrrolidone, e.g., alkyl vinyl imidazolium, alkyl vinylpyridinium, alkyl vinyl pyrrolidone salts.

Other suitable cationic polymers for use in the compositions includecopolymers of 1-vinyl-2-pyrrolidone and 1-vinyl-3-methylimidazolium salt(e.g., chloride salt) (referred to in the industry by the Cosmetic,Toiletry, and Fragrance Association, “CTFA”, as Polyquaternium-16);copolymers of 1-vinyl-2-pyrrolidone and dimethylaminoethyl methacrylate(referred to in the industry by CTFA as Polyquaternium-11); cationicdiallyl quaternary ammonium-containing polymers, including, for example,dimethyldiallylammonium chloride homopolymer, copolymers of acrylamideand dimethyldiallylammonium chloride (referred to in the industry byCTFA as Polyquaternium 6 and Polyquaternium 7, respectively); amphotericcopolymers of acrylic acid including copolymers of acrylic acid anddimethyldiallylammonium chloride (referred to in the industry by CTFA asPolyquaternium 22), terpolymers of acrylic acid withdimethyldiallylammonium chloride and acrylamide (referred to in theindustry by CTFA as Polyquaternium 39), and terpolymers of acrylic acidwith methacrylamidopropyl trimethylammonium chloride and methylacrylate(referred to in the industry by CTFA as Polyquaternium 47). Preferredcationic substituted monomers are the cationic substituteddialkylaminoalkyl acrylamides, dialkylaminoalkyl methacrylamides, andcombinations thereof. A non limiting example ispolymethyacrylamidopropyl trimonium chloride, available under the tradename Polycare 133, from Rhone-Poulenc.

Other suitable cationic polymers for use in the composition includepolysaccharide polymers, such as cationic cellulose derivatives andcationic starch derivatives.

Preferred cationic cellulose polymers are salts of hydroxyethylcellulose reacted with trimethyl ammonium substituted epoxide, referredto in the industry (CTFA) as Polyquaternium 10 and available fromAmerchol Corp. (Edison, N.J., USA) in their Polymer LR, JR, and KGseries of polymers. Other suitable types of cationic cellulose includesthe polymeric quaternary ammonium salts of hydroxyethyl cellulosereacted with lauryl dimethyl ammonium-substituted epoxide referred to inthe industry (CTFA) as Polyquaternium 24. These materials are availablefrom Amerchol Corp. under the tradename Polymer LM-200.

Other suitable cationic polymers include cationic guar gum derivatives,such as guar hydroxypropyltrimonium chloride, specific examples of whichinclude the Jaguar series commercially available from Rhone-PoulencIncorporated and the N-Hance series commercially available from AqualonDivision of Hercules, Inc. Other suitable cationic polymers includequaternary nitrogen-containing cellulose ethers, some examples of whichare described in U.S. Pat. No. 3,962,418. Other suitable cationicpolymers include copolymers of etherified cellulose, guar and starch,some examples of which are described in U.S. Pat. No. 3,958,581. Whenused, the cationic polymers herein are either soluble in the compositionor are soluble in a complex coacervate phase in the composition formedby the cationic polymer and the anionic, amphoteric and/or zwitterionicdetersive surfactant component described hereinbefore. Complexcoacervates of the cationic polymer can also be formed with othercharged materials in the composition.

b) Anionic Polymers

Examples of anionic polymers are copolymers of vinyl acetate andcrotonic acid, terpolymers of vinyl acetate, crotonic acid and a vinylester of an alpha-branched saturated aliphatic monocarboxylic acid suchas vinyl neodecanoate; and copolymers of methyl vinyl ether and maleicanhydride, acrylic copolymers and terpolymers containing acrylic acid ormethacrylic acid.

Examples of anionic monomers include unsaturated carboxylic acidmonomers such as acrylic acid, methacrylic acid, maleic acid, maleicacid half ester, itaconic acid, fumeric acid, and crotonic acid; halfesters of an unsaturated polybasic acid anhydride such as succinicanhydride, phthalic anhydride or the like with a hydroxylgroup-containing acrylate and/or methacrylate such as hydroxyethylacrylate and, hydroxyethyl methacrylate, hydroxypropyl acrylate and thelike; monomers having a sulfonic acid group such as styrenesulfonicacid, sulfoethyl acrylate and methacrylate, and the like; and monomershaving a phosphoric acid group such as acid phosphooxyethyl acrylate andmethacrylate, 3-chloro-2-acid phosphooxypropyl acrylate andmethacrylate, and the like.

c) Amphoteric Monomers

Examples of the amphoteric monomers include zwitterionized derivativesof the aforementioned amine derivatives of (meth)acrylic acids or theamine derivatives of (meth)acrylamide such as dimethylaminoethyl(meth)acrylate, dimethylaminopropyl(meth)acrylamide by a halogenatedfatty acid salt such as potassium monochloroacetate, sodiummonobromopropionate, aminomethylpropanol salt of monochloroacetic acid,triethanolamine salts of monochloroacetic acid and the like; and aminederivatives of (meth)acrylic acid or (meth)acrylamide, as discussedabove, modified with propanesultone.

36) Nonionic Polymers

The compositions herein can comprise nonionic polymers. For instance,polyalkylene glycols having a molecular weight of more than about 1000can be used. Preferred polyethylene glycol polymers can include PEG-2M(also known as Polyox WSR® N-10, which is available from Union Carbideand as PEG-2,000); PEG-5M (also known as Polyox WSR® N-35 and PolyoxWSR® N-80, available from Union Carbide and as PEG-5,000 andPolyethylene Glycol 300,000); PEG-7M (also known as Polyox WSR® N-750available from Union Carbide); PEG-9M (also known as Polyox WSR® N-3333available from Union Carbide); and PEG-14 M (also known as Polyox WSR®N-3000 available from Union Carbide).

Examples of nonionic monomers are acrylic or methacrylic acid esters ofC1-C24 alcohols, such as methanol, ethanol, 1-propanol, 2-propanol,1-butanol, 2-methyl-1-propanol, 1-pentanol, 2-pentanol, 3-pentanol,2-methyl-1-butanol, 1-methyl-1-butanol, 3-methyl-1-butanol,1-methyl-1-pentanol, 2-methyl-1-pentanol, 3-methyl-1-pentanol,t-butanol, cyclohexanol, 2-ethyl-1-butanol, 3-heptanol, benzyl alcohol,2-octanol, 6-methyl-1-heptanol, 2-ethyl-1-hexanol,3,5-dimethyl-1-hexanol, 3,5,5-trimethyl-1-hexanol, 1-decanol,1-dodecanol, 1-hexadecanol, 1-octadecanol, styrene, chlorostyrene, vinylesters such as vinyl acetate, vinyl chloride, vinylidene chloride,acrylonitrile, alpha-methylstyrene, t-butylstyrene, butadiene,cyclohexadiene, ethylene, propylene, vinyl toluene, alkoxyalkyl(meth)acrylate, methoxy ethyl (meth)acrylate, butoxyethyl(meth)acrylate, allyl acrylate, allyl methacrylate, cyclohexyl acrylateand methacrylate, oleyl acrylate and methacrylate, benzyl acrylate andmethacrylate, tetrahydrofurfuryl acrylate and methacrylate, ethyleneglycol di-acrylate and -methacrylate, 1,3-butyleneglycol di-acrylate and-methacrylate, diacetonacrylamide, isobornyl (meth)acrylate, n-butylmethacrylate, isobutyl methacrylate, 2-ethylhexyl methacrylate, methylmethacrylate, t-butylacrylate, t-butylmethacrylate, and mixtures thereof

37) Hair Conditioning Agents

Conditioning agents include any material which is used to give aparticular conditioning benefit to keratinous tissue. For instance, inhair treatment compositions, suitable conditioning agents include thosewhich deliver one or more benefits relating to shine, softness,combability, antistatic properties, wet-handling, damage, manageability,body, and greasiness. Conditioning agents useful in the compositions ofthe present invention can comprise a water insoluble, water dispersible,non-volatile liquid that forms emulsified, liquid particles. Suitableconditioning agents for use in the composition include thoseconditioning agents characterized generally as silicones (e.g., siliconeoils, cationic silicones, silicone gums, high refractive silicones, andsilicone resins), organic conditioning oils (e.g., hydrocarbon oils,polyolefins, and fatty esters) or combinations thereof, or thoseconditioning agents which otherwise form liquid, dispersed particles inthe aqueous surfactant matrix herein.

When included, the concentration of the conditioning agent in thecomposition can be sufficient to provide the desired conditioningbenefits, and as will be apparent to one of ordinary skill in the art.Such concentration can vary with the conditioning agent, theconditioning performance desired, the average size of the conditioningagent particles, the type and concentration of other components, andother like factors.

a) Silicones

The conditioning agent of the compositions of the present invention ispreferably an insoluble silicone conditioning agent. The siliconeconditioning agent particles may comprise volatile silicone,non-volatile silicone, or combinations thereof. Non-volatile siliconconditioning agents are preferred. If volatile silicones are present, itwill typically be incidental to their use as a solvent or carrier forcommercially available forms of non-volatile silicone materialsingredients, such as silicone gums and resins. The silicone conditioningagent particles may comprise a silicone fluid conditioning agent and mayalso comprise other ingredients, such as a silicone resin to improvesilicone fluid deposition efficiency or enhance glossiness of the hair.

The concentration of the silicone conditioning agent typically rangesfrom about 0.01% to about 10%, preferably from about 0.1% to about 8%,more preferably from about 0.1% to about 5%, more preferably from about0.2% to about 3%. Non-limiting examples of suitable siliconeconditioning agents, and optional suspending agents for the silicone,are described in U.S. Reissue Pat. No. 34,584, U.S. Pat. No. 5,104,646,and U.S. Pat. No. 5,106,609.

Background material on silicones including sections discussing siliconefluids, gums, and resins, as well as manufacture of silicones, are foundin Encyclopedia of Polymer Science and Engineering, vol. 15, 2d ed., pp204-308, John Wiley & Sons, Inc. (1989).

b) Silicone Oils

Silicone fluids include silicone oils, which are flowable siliconematerials having a viscosity, as measured at 25° C., less than 1,000,000csk, preferably from about 5 csk to about 1,000,000 csk, more preferablyfrom about 100 csk to about 600,000 csk. Suitable silicone oils for usein the compositions of the present invention include polyalkylsiloxanes, polyaryl siloxanes, polyalkylaryl siloxanes, polyethersiloxane copolymers, and mixtures thereof. Other insoluble, non-volatilesilicone fluids having hair conditioning properties may also be used.

c) Amino and Cationic Silicones

Cationic silicone fluids suitable for use in the compositions of thepresent invention include, but are not limited to, the polymer known as“trimethylsilylamodimethicone”.

Other silicone cationic polymers which may be used in the compositionsof the present invention may be UCARE SILICONE ALE 56™, available fromUnion Carbide.

d) Silicone Gums

Other silicone fluids suitable for use in the compositions of thepresent invention are the insoluble silicone gums. These gums arepolyorganosiloxane materials having a viscosity, as measured at 25° C.,of greater than or equal to 1,000,000 csk. Silicone gums are describedin U.S. Pat. No. 4,152,416; Noll and Walter, Chemistry and Technology ofSilicones, New York: Academic Press (1968); and in General ElectricSilicone Rubber Product Data Sheets SE 30, SE 33, SE 54 and SE 76.Specific non-limiting examples of silicone gums for use in thecompositions of the present invention include polydimethylsiloxane,(polydimethylsiloxane) (methylvinylsiloxane) copolymer,poly(dimethylsiloxane) (diphenyl siloxane)(methylvinylsiloxane)copolymer and mixtures thereof.

e) High Refractive Index Silicones

Other non-volatile, insoluble silicone fluid conditioning agents thatare suitable for use in the compositions of the present invention arethose known as “high refractive index silicones,” having a refractiveindex of at least about 1.46, preferably at least about 1.48, morepreferably at least about 1.52, more preferably at least about 1.55. Therefractive index of the polysiloxane fluid will generally be less thanabout 1.70, typically less than about 1.60. In this context,polysiloxane “fluid” includes oils as well as gums.

When high refractive index silicones are used in the compositions of thepresent invention, they are preferably used in solution with a spreadingagent, such as a silicone resin or a surfactant, to reduce the surfacetension by a sufficient amount to enhance spreading and thereby enhancethe glossiness (subsequent to drying) of hair treated with thecompositions.

Silicone fluids suitable for use in the compositions of the presentinvention are disclosed in U.S. Pat. No. 2,826,551, U.S. Pat. No.3,964,500, U.S. Pat. No. 4,364,837, GB849433, and Silicon Compounds,Petrarch Systems, Inc. (1984).

f) Silicone Resins

Silicone resins may be included in the silicone conditioning agent ofthe compositions of the present invention. These resins are highlycross-linked polymeric siloxane systems. The cross-linking is introducedthrough the incorporation of trifunctional and tetrafunctional silaneswith monofunctional or difunctional, or both, silanes during manufactureof the silicone resin.

38) Organic Conditioning Oils

Compositions of the present invention may also comprise organicconditioning oil. In one embodiment, from about 0.05% to about 20%,preferably from about 0.08% to about 1.5%, more preferably from about0.1% to about 1%, of at least one organic conditioning oil is includedas a conditioning agent, either alone or in combination with otherconditioning agents, such as the silicones (described herein).

a) Hydrocarbon Oils

Suitable organic conditioning oils for use as conditioning agents in thecompositions of the present invention include, but are not limited to,hydrocarbon oils having at least about 10 carbon atoms, such as cyclichydrocarbons, straight chain aliphatic hydrocarbons (saturated orunsaturated), and branched chain aliphatic hydrocarbons (saturated orunsaturated), including polymers and mixtures thereof. Straight chainhydrocarbon oils preferably are from about C12 to about C19. Branchedchain hydrocarbon oils, including hydrocarbon polymers, typically willcontain more than 19 carbon atoms.

Specific non-limiting examples of these hydrocarbon oils includeparaffin oil, mineral oil, saturated and unsaturated dodecane, saturatedand unsaturated tridecane, saturated and unsaturated tetradecane,saturated and unsaturated pentadecane, saturated and unsaturatedhexadecane, polybutene, polydecene, and mixtures thereof. Branched-chainisomers of these compounds, as well as of higher chain lengthhydrocarbons, can also be used, examples of which include highlybranched, saturated or unsaturated, alkanes such as thepermethyl-substituted isomers, e.g., the permethyl-substituted isomersof hexadecane and eicosane, such as2,2,4,4,6,6,8,8-dimethyl-10-methylundecane and2,2,4,4,6,6-dimethyl-8-methylnonane, available from PermethylCorporation, hydrocarbon polymers such as polybutene and polydecene. Apreferred hydrocarbon polymer is polybutene, such as the copolymer ofisobutylene and butene. A commercially available material of this typeis L-14 polybutene from Amoco Chemical Corporation.

b) Polyolefins

Organic conditioning oils for use in the compositions of the presentinvention can also include liquid polyolefins, more preferably liquidpoly-α-olefins, more preferably hydrogenated liquid poly-α-olefins.Polyolefins for use herein are prepared by polymerization of C4 to aboutC14 olefenic monomers, preferably from about C6 to about C12.

Preferred non-limiting examples of olefenic monomers for use inpreparing the polyolefin liquids herein include ethylene, propylene,1-butene, 1-pentene, 1-hexene to 1-hexadecenes, 1-octene, 1-decene,1-dodecene, 1-tetradecene, branched chain isomers such as4-methyl-1-pentene, and mixtures thereof. Also suitable for preparingthe polyolefin liquids are olefin-containing refinery feedstocks oreffluents.

c) Fatty Esters

Other suitable organic conditioning oils for use as the conditioningagent in the compositions of the present invention include, but are notlimited to, fatty esters having at least 10 carbon atoms. These fattyesters include esters with hydrocarbyl chains derived from fatty acidsor alcohols (e.g. mono-esters, polyhydric alcohol esters, and di- andtri-carboxylic acid esters). The hydrocarbyl radicals of the fattyesters hereof may include or have covalently bonded thereto othercompatible functionalities, such as amides and alkoxy moieties (e.g.,ethoxy or ether linkages, etc.).

Specific examples of preferred fatty esters include, but are not limitedto: isopropyl isostearate, hexyl laurate, isohexyl laurate, isohexylpalmitate, isopropyl palmitate, decyl oleate, isodecyl oleate, hexadecylstearate, decyl stearate, isopropyl isostearate, dihexyldecyl adipate,lauryl lactate, myristyl lactate, cetyl lactate, oleyl stearate, oleyloleate, oleyl myristate, lauryl acetate, cetyl propionate, and oleyladipate.

Other fatty esters suitable for use in the compositions of the presentinvention are mono-carboxylic acid esters of the general formula R′COOR,wherein R′ and R are alkyl or alkenyl radicals, and the sum of carbonatoms in R′ and R is at least 10, preferably at least 22.

Still other fatty esters suitable for use in the compositions of thepresent invention are di- and tri-alkyl and alkenyl esters of carboxylicacids, such as esters of C4 to C8 dicarboxylic acids (e.g. C1 to C22esters, preferably C1 to C6, of succinic acid, glutaric acid, and adipicacid). Specific non-limiting examples of di- and tri-alkyl and alkenylesters of carboxylic acids include isocetyl stearyol stearate,diisopropyl adipate, and tristearyl citrate.

Other fatty esters suitable for use in the compositions of the presentinvention are those known as polyhydric alcohol esters. Such polyhydricalcohol esters include alkylene glycol esters, such as ethylene glycolmono and di-fatty acid esters, diethylene glycol mono- and di-fatty acidesters, polyethylene glycol mono- and di-fatty acid esters, propyleneglycol mono- and di-fatty acid esters, polypropylene glycol monooleate,polypropylene glycol 2000 monostearate, ethoxylated propylene glycolmonostearate, glyceryl mono- and di-fatty acid esters, polyglycerolpoly-fatty acid esters, ethoxylated glyceryl monostearate, 1,3-butyleneglycol monostearate, 1,3-butylene glycol distearate, polyoxyethylenepolyol fatty acid ester, sorbitan fatty acid esters, and polyoxyethylenesorbitan fatty acid esters.

Still other fatty esters suitable for use in the compositions of thepresent invention are glycerides, including, but not limited to, mono-,di-, and tri-glycerides, preferably di- and tri-glycerides, morepreferably triglycerides. For use in the compositions described herein,the glycerides are preferably the mono-, di-, and tri-esters of glyceroland long chain carboxylic acids, such as C10 to C22 carboxylic acids. Avariety of these types of materials can be obtained from vegetable andanimal fats and oils, such as castor oil, safflower oil, cottonseed oil,corn oil, olive oil, cod liver oil, almond oil, avocado oil, palm oil,sesame oil, lanolin and soybean oil. Synthetic oils include, but are notlimited to, triolein and tristearin glyceryl dilaurate.

Other fatty esters suitable for use in the compositions of the presentinvention are water insoluble synthetic fatty esters.

Specific non-limiting examples of suitable synthetic fatty esters foruse in the compositions of the present invention include: P-43 (C8-C10triester of trimethylolpropane), MCP-684 (tetraester of 3,3diethanol-1,5 pentadiol), MCP 121 (C8-C10 diester of adipic acid), allof which are available from Mobil Chemical Company.

39) Anti-Dandruff Actives

The compositions of the present invention may also contain ananti-dandruff agent. Suitable, non-limiting examples of anti-dandruffparticulates include: pyridinethione salts, azoles, selenium sulfide,particulate sulfur, and mixtures thereof. Preferred are pyridinethionesalts, especially 1-hydroxy-2-pyridinethione salts. The concentration ofpyridinethione anti-dandruff particulate typically ranges from about0.1% to about 4%, by weight of the composition, preferably from about0.1% to about 3%, more preferably from about 0.3% to about 2%. Preferredpyridinethione salts include those formed from heavy metals such aszinc, tin, cadmium, magnesium, aluminum and zirconium, preferably zinc,more preferably the zinc salt of 1-hydroxy-2-pyridinethione (known as“zinc pyridinethione” or “ZPT”). Pyridinethione anti-dandruff agents aredescribed, for example, in U.S. Pat. No. 2,809,971; U.S. Pat. No.3,236,733; U.S. Pat. No. 3,753,196; U.S. Pat. No. 3,761,418; U.S. Pat.No. 4,345,080; U.S. Pat. No. 4,323,683; U.S. Pat. No. 4,379,753 and U.S.Pat. No. 4,470,982.

40) Humectant

The compositions of the present invention may contain a humectant.Humectants can be selected from the group consisting of polyhydricalcohols, water soluble alkoxylated nonionic polymers, and mixturesthereof. Humectants, when used herein, are preferably used at levels offrom about 0.1% to about 20%, more preferably from about 0.5% to about5%.

Polyhydric alcohols useful herein include glycerin, sorbitol, propyleneglycol, butylene glycol, hexylene glycol, ethoxylated glucose,1,2-hexane diol, hexanetriol, dipropylene glycol, erythritol, trehalose,diglycerin, xylitol, maltitol, maltose, glucose, fructose, sodiumchondroitin sulfate, sodium hyaluronate, sodium adenosine phosphate,sodium lactate, pyrrolidone carbonate, glucosamine, cyclodextrin, andmixtures thereof.

Water soluble alkoxylated nonionic polymers useful herein includepolyethylene glycols and polypropylene glycols having a molecular weightof up to about 1000 such as those with CTFA names PEG-200, PEG-400,PEG-600, PEG-1000, and mixtures thereof.

41) Suspending Agent

The compositions of the present invention may further comprise asuspending agent, preferably at concentrations effective for suspendingwater-insoluble material in dispersed form in the compositions or formodifying the viscosity of the composition. Such concentrations canpreferably range from about 0.1% to about 10%, more preferably fromabout 0.3% to about 5.0%.

Suspending agents useful herein include anionic polymers and nonionicpolymers. Useful herein are vinyl polymers such as cross linked acrylicacid polymers with the CTFA name Carbomer, cellulose derivatives andmodified cellulose polymers such as methyl cellulose, ethyl cellulose,nitro cellulose, sodium carboxymethyl cellulose, crystalline cellulose,cellulose powder, polyvinylpyrrolidone, polyvinyl alcohol, guar gum,hydroxypropyl guar gum, arabia gum, galactan, carob gum, pectin, agar,quince seed (Cydonia oblonga Mill), starch (rice, corn, potato, wheat),algae colloids (algae extract), microbiological polymers such asdextran, succinoglucan, pulleran, starch-based polymers such ascarboxymethyl starch, methylhydroxypropyl starch, alginic acid-basedpolymers such as sodium alginate, alginic acid propylene glycol esters,acrylate polymers such as sodium polyacrylate, polyethylacrylate,polyacrylamide, polyethyleneimine, and inorganic water soluble materialsuch as bentonite, aluminum magnesium silicate, laponite, hectonite, andanhydrous silicic acid. Actives aforementioned as thickening agents canalso be used herein as suspending agents.

Commercially available viscosity modifiers highly useful herein includeCarbomers with tradenames Carbopol 934, Carbopol 940, Carbopol 950,Carbopol 980, and Carbopol 981, all available from B. F. GoodrichCompany, acrylates/steareth-20 methacrylate copolymer with tradenameACRYSOL 22 available from Rohm and Hass, nonoxynyl hydroxyethylcellulosewith tradename AMERCELL POLYMER HM-1500 available from Amerchol,methylcellulose with tradename BENECEL, hydroxyethyl cellulose withtradename NATROSOL, hydroxypropyl cellulose with tradename KLUCEL, cetylhydroxyethyl cellulose with tradename POLYSURF 67, all supplied byHercules, ethylene oxide and/or propylene oxide based polymers withtradenames CARBOWAX PEGs, POLYOX WASRs, and UCON FLUIDS, all supplied byAmerchol.

Other optional suspending agents include crystalline suspending agentswhich can be categorized as acyl derivatives, long chain amine oxides,long chain acyl derivatives and mixtures thereof. These suspendingagents are described in U.S. Pat. No. 4,741,855. These preferredsuspending agents include ethylene glycol esters of fatty acids, alkanolamides of fatty acids, long chain esters of long chain fatty acids(e.g., stearyl stearate, cetyl palmitate, etc.); long chain esters oflong chain alkanol amides (e.g., stearamide diethanolamide distearate,stearamide monoethanolamide stearate); and glyceryl esters (e.g.,glyceryl distearate, trihydroxystearin, tribehenin) a commercial exampleof which is Thixin® available from Rheox, Inc

Other suitable suspending agents include primary amines having a fattyalkyl moiety having at least about 16 carbon atoms, examples of whichinclude palmitamine or stearamine, and secondary amines having two fattyalkyl moieties each having at least about 12 carbon atoms, examples ofwhich include dipalmitoylamine or di(hydrogenated tallow)amine. Stillother suitable suspending agents include di(hydrogenated tallow)phthalicacid amide, and crosslinked maleic anhydride-methyl vinyl ethercopolymer.

42) Terpene Alcohol

The compositions of the present invention may comprise a terpene alcoholor combinations of terpene alcohols. As used herein, “terpene alcohol”refers to organic compounds composed of two or more 5-carbon isopreneunits [CH2=C(CH3)-CH═CH2] with a terminal hydroxyl group. Preferably,the composition can comprise from about 0.001% to about 50%, preferablyfrom about 0.01% to about 20%, more preferably from about 0.1% to about15%, even more preferably from about 0.1% to about 10%, still morepreferably from about 0.5% to about 5%, and still more preferably fromabout 1% to about 5%, by weight of the composition, of the terpenealcohol.

Examples of terpene alcohols that can be useful herein include farnesol,derivatives of farnesol, isomers of farnesol, geraniol, derivatives ofgeraniol, isomers of geraniol, phytantriol, derivatives of phytantriol,isomers of phytantriol, and mixtures thereof. A preferred terpenealcohol for use herein is farnesol.

a) Farnesol and Derivatives Thereof

Farnesol is a naturally occurring substance which is believed to act asa precursor and/or intermediate in the biosynthesis of squalene andsterols, especially cholesterol. Farnesol is also involved in proteinmodification and regulation (e.g., farnesylation of proteins), and thereis a cell nuclear receptor which is responsive to farnesol.

Chemically, farnesol is [2E,6E]-3,7,11-trimethyl-2,6,10-dodecatrien-1-oland as used herein “farnesol” includes isomers and tautomers of such.Farnesol is commercially available, e.g., under the names farnesol (amixture of isomers from Dragoco) and trans-trans-farnesol (SigmaChemical Company). A suitable derivative of farnesol is farnesyl acetatewhich is commercially available from Aldrich Chemical Company.

b) Geraniol and Derivatives Thereof

Geraniol is the common name for the chemical known as3,7-dimethyl-2,6-octadien-1-ol. As used herein, “geraniol” includesisomers and tautomers of such. Geraniol is commercially available fromAldrich Chemical Company. Suitable derivatives of geraniol includegeranyl acetate, geranylgeraniol, geranyl pyrophosphate, andgeranylgeranyl pyrophosphate, all of which are commercially availablefrom Sigma Chemical Company. For example, geraniol is useful as a spidervessel/red blotchiness repair agent, a dark circle/puffy eye repairagent, sallowness repair agent, a sagging repair agent, an anti-itchagent, a skin thickening agent, a pore reduction agent, oil/shinereduction agent, a post-inflammatory hyperpigmentation repair agent,wound treating agent, an anti-cellulite agent, and regulating skintexture, including wrinkles and fine lines.

c) Phytantriol and Derivatives Thereof

Phytantriol is the common name for the chemical known as 3,7,11,15,tetramethylhexadecane-1,2,3,-triol. Phytantriol is commerciallyavailable from BASF. For example, phytantriol is useful as a spidervessel/red blotchiness repair agent, a dark circle/puffy eye repairagent, sallowness repair agent, a sagging repair agent, an anti-itchagent, a skin thickening agent, a pore reduction agent, oil/shinereduction agent, a post-inflammatory hyperpigmentation repair agent,wound treating agent, an anti-cellulite agent, and regulating skintexture, including wrinkles and fine lines.

43) Enzymes, Enzyme Inhibitors and Enzyme activators (Coenzymes)

The compositions of the present invention may contain a safe andeffective amount of one or more enzymes, enzyme inhibitors or enzymeactivators (coenzymes). Examples of enzymes are lipases, proteases,catalase, superoxide-dismutase, amylases, glucuronidases, peroxidases,in particular glutathione peroxidase or lactoperoxidase, ceramidases,hyaluronidases. All of these enzymes may be obtained by extraction or byfermentation biotechnology processes. Examples of enzyme inhibitorsinclude trypsine inhibitors, Bowmann Birk inhibitor, chymotrypsininhibitors, botanical extracts with or without tannins, flavonoids,quercetin which inhibit enzymatic activity. Enzyme preparations can befound, for instance, in the product named VENUCEANE proposed by SEDERMA,France (WO 02/066668). Enzyme activators and coenzymes include CoenzymeA, coenzyme Q10 (ubiquinone), glycyrrhizidine, berberine, chrysine.

II CARRIER

The compositions of the present invention can comprise an orally or adeimatologically acceptable carrier, or injectible liquid, dependingupon the desired product form.

A. Dermatologically Acceptable Carrier

The topical compositions of the present invention can also comprise adermatologically acceptable carrier for the composition. In oneembodiment, the carrier is present at a level of from about 50% to about99.99%, preferably from about 60% to about 99.9%, more preferably fromabout 70% to about 98%, and even more preferably from about 80% to about95%, by weight of the composition.

The carrier can be in a wide variety of forms. Non-limiting examplesinclude simple solutions (water or oil based), emulsions, and solidforms (gels, sticks). For example, emulsion carriers can include, butare not limited to, oil-in-water, water-in-oil, water-in-silicone,water-in-oil-in-water, and oil-in-water-in-silicone emulsions.

Depending upon the desired product form, preferred carriers can comprisean emulsion such as oil-in-water emulsions (e.g., silicone in water) andwater-in-oil emulsions, (e.g., water-in-silicone emulsions). As will beunderstood by the skilled artisan, a given component will distributeprimarily into either the water or oil phase, depending on the watersolubility/dispensability of the component in the composition. In oneembodiment, oil-in-water emulsions are especially preferred.

Emulsions according to the present invention can contain an aqueousphase and a lipid or oil. Lipids and oils may be derived from animals,plants, or petroleum and may be natural or synthetic (i.e., man-made).Preferred emulsions can also contain a humectant, such as glycerin.Emulsions can further comprise from about 0.1% to about 10%, morepreferably from about 0.2% to about 5%, of an emulsifier, based on theweight of the composition. Emulsifiers may be nonionic, anionic orcationic. Suitable emulsifiers are disclosed in, for example, U.S. Pat.No. 3,755,560, U.S. Pat. No. 4,421,769, and McCutcheon's Detergents andEmulsifiers, North American Edition, pages 317-324 (1986). Suitableemulsions may have a wide range of viscosities, depending on the desiredproduct form.

The compositions of the present invention can be in the form of pourableliquids (under ambient conditions). The compositions can thereforecomprise an aqueous carrier, which is typically present at a level offrom about 20% to about 95%, preferably from about 60% to about 85%. Theaqueous carrier may comprise water, or a miscible mixture of water andorganic solvent, but preferably comprises water with minimal or nosignificant concentrations of organic solvent, except as otherwiseincidentally incorporated into the composition as minor ingredients ofother essential or optional components.

The emulsion may also contain an anti-foaming agent to minimize foamingupon application to the keratinous tissue. Anti-foaming agents includehigh molecular weight silicones and other materials well known in theart for such use.

Preferred water-in-silicone and oil-in-water emulsions are described ingreater detail below.

1) Water-in-Silicone Emulsion

Water-in-silicone emulsions contain a continuous silicone phase and adispersed aqueous phase.

a) Continuous Silicone Phase

Preferred water-in-silicone emulsions of the present invention containfrom about 1% to about 60%, preferably from about 5% to about 40%, morepreferably from about 10% to about 20%, by weight of a continuoussilicone phase. The continuous silicone phase exists as an externalphase that contains or surrounds the discontinuous aqueous phasedescribed hereinafter.

The continuous silicone phase contains a polyorganosiloxane oil. Apreferred water-in-silicone emulsion system is formulated to provide anoxidatively stable vehicle for the active ingredients of the presentinvention. The continuous silicone phase of these preferred emulsionscontain between about 50% and about 99.9% by weight oforganopolysiloxane oil and less than about 50% by weight of anon-silicone oil. In an especially preferred embodiment, the continuoussilicone phase contains at least about 50%, preferably from about 60% toabout 99.9%, more preferably from about 70% to about 99.9%, and evenmore preferably from about 80% to about 99.9%, polyorganosiloxane oil byweight of the continuous silicone phase, and up to about 50%non-silicone oils, preferably less about 40%, more preferably less thanabout 30%, even more preferably less than about 10%, and even morepreferably less than about 2%, by weight of the continuous siliconephase.

The organopolysiloxane oil for use in the composition may be volatile,non-volatile, or a mixture of volatile and non-volatile silicones. Theterm “nonvolatile” as used in this context refers to those siliconesthat are liquid under ambient conditions and have a flash point (underone atmospheric of pressure) of or greater than about 100° C. The term“volatile” as used in this context refers to all other silicone oils.Suitable organopolysiloxanes can be selected from a wide variety ofsilicones spanning a broad range of volatilities and viscosities.Examples of suitable organopolysiloxane oils include polyalkylsiloxanes,cyclic polyalkylsiloxanes, and polyalkylarylsiloxanes.

Polyalkylsiloxanes useful in the composition herein includepolyalkylsiloxanes with viscosities of from about 0.5 to about 1,000,000centistokes at 25° C. Commercially available polyalkylsiloxanes includethe polydimethylsiloxanes, which are also known as dimethicones,examples of which include the Vicasil® series sold by General ElectricCompany and the Dow Corning® 200 series sold by Dow Corning Corporation.Specific examples of suitable polydimethylsiloxanes include Dow Corning®200 fluid, Dow Corning® 225 fluid, and Dow Corning® 200 fluids Examplesof suitable alkyl-substituted dimethicones include cetyl dimethicone andlauryl dimethicone.

Cyclic polyalkylsiloxanes suitable for use in the composition includecommercially available cyclomethicones such as Dow Corning® 244 fluid,Dow Corning® 344 fluid, Dow Corning® 245 fluid and Dow Corning® 345fluid.

Also useful are materials such as trimethylsiloxysilicate. Acommercially available trimethylsiloxysilicate is sold as a mixture withdimethicone as Dow Corning® 593 fluid.

Dimethiconols are also suitable for use in the composition. Commerciallyavailable dimethiconols are typically sold as mixtures with dimethiconeor cyclomethicone (e.g. Dow Corning® 1401, 1402, and 1403 fluids).

Polyalkylaryl siloxanes are also suitable for use in the composition.Polymethylphenyl siloxanes having viscosities from about 15 to about 65centistokes at 25° C. are especially useful.

Preferred for use herein are organopolysiloxanes selected frompolyalkylsiloxanes, alkyl substituted dimethicones, cyclomethicones,trimethylsiloxysilicates, dimethiconols, polyalkylaryl siloxanes, andmixtures thereof. More preferred for use herein are polyalkylsiloxanesand cyclomethicones. Preferred among the polyalkylsiloxanes aredimethicones.

As stated above, the continuous silicone phase may contain one or morenon-silicone oils. Suitable non-silicone oils have a melting point ofabout 25° C. or less under about one atmosphere of pressure. Examples ofnon-silicone oils suitable for use in the continuous silicone phase arethose well known in the chemical arts in topical personal care productsin the form of water-in-oil emulsions, e.g., mineral oil, vegetableoils, synthetic oils, semisynthetic oils, etc.

b) Dispersed Aqueous Phase

The topical compositions of the present invention contain from about 30%to about 90%, more preferably from about 50% to about 85%, and stillmore preferably from about 70% to about 80% of a dispersed aqueousphase. In emulsion technology, the term “dispersed phase” is a termwell-known to one skilled in the art which means that the phase existsas small particles or droplets that are suspended in and surrounded by acontinuous phase. The dispersed phase is also known as the internal ordiscontinuous phase. The dispersed aqueous phase is a dispersion ofsmall aqueous particles or droplets suspended in and surrounded by thecontinuous silicone phase described hereinbefore.

The aqueous phase can be water, or a combination of water and one ormore water soluble or dispersible ingredients. Nonlimiting examples ofsuch ingredients include thickeners, acids, bases, salts, chelants,gums, water-soluble or dispersible alcohols and polyols, buffers,preservatives, sunscreening agents, colorings, and the like.

The topical compositions of the present invention will typically containfrom about 25% to about 90%, preferably from about 40% to about 80%,more preferably from about 60% to about 80%, water in the dispersedaqueous phase by weight of the composition.

c) Emulsifier for Dispersing the Aqueous Phase

The water-in-silicone emulsions of the present invention preferablycontain an emulsifier. In a preferred embodiment, the compositioncontains from about 0.1% to about 10% emulsifier, more preferably fromabout 0.5% to about 7.5%, still more preferably from about 1% to about5%, emulsifier by weight of the composition. The emulsifier helpsdisperse and suspend the aqueous phase within the continuous siliconephase.

A wide variety of emulsifying agents can be employed herein to form thepreferred water-in-silicone emulsion. Known or conventional emulsifyingagents can be used in the composition, provided that the selectedemulsifying agent is chemically and physically compatible withcomponents of the composition of the present invention, and provides thedesired dispersion characteristics. Suitable emulsifiers includesilicone emulsifiers, non-silicon-containing emulsifiers, and mixturesthereof, known by those skilled in the art for use in topical personalcare products. Preferably these emulsifiers have an HLB value of or lessthan about 14, more preferably from about 2 to about 14, and still morepreferably from about 4 to about 14. Emulsifiers having an HLB valueoutside of these ranges can be used in combination with otheremulsifiers to achieve an effective weighted average HLB for thecombination that falls within these ranges.

Silicone emulsifiers are preferred. A wide variety of siliconeemulsifiers are useful herein. These silicone emulsifiers are typicallyorganically modified organopolysiloxanes, also known to those skilled inthe art as silicone surfactants. Useful silicone emulsifiers includedimethicone copolyols. These materials are polydimethyl siloxanes whichhave been modified to include polyether side chains such as polyethyleneoxide chains, polypropylene oxide chains, mixtures of these chains, andpolyether chains containing moieties derived from both ethylene oxideand propylene oxide. Other examples include alkyl-modified dimethiconecopolyols, i.e., compounds which contain C2-C30 pendant side chains.Still other useful dimethicone copolyols include materials havingvarious cationic, anionic, amphoteric, and zwitterionic pendantmoieties.

Nonlimiting examples of dimethicone copolyols and other siliconesurfactants useful as emulsifiers herein include polydimethylsiloxanepolyether copolymers with pendant polyethylene oxide sidechains,polydimethylsiloxane polyether copolymers with pendant polypropyleneoxide sidechains, polydimethylsiloxane polyether copolymers with pendantmixed polyethylene oxide and polypropylene oxide sidechains,polydimethylsiloxane polyether copolymers with pendant mixedpoly(ethylene)(propylene)oxide sidechains, polydimethylsiloxanepolyether copolymers with pendant organobetaine sidechains,polydimethylsiloxane polyether copolymers with pendant carboxylatesidechains, polydimethylsiloxane polyether copolymers with pendantquaternary ammonium sidechains; and also further modifications of thepreceding copolymers containing pendant C2-C30 straight, branched, orcyclic alkyl moieties. Examples of commercially available dimethiconecopolyols useful herein sold by Dow Corning Corporation are Dow Corning®190, 193, Q2-5220, 2501 Wax, 2-5324 fluid, and 3225C (this latermaterial being sold as a mixture with cyclomethicone). Cetyl dimethiconecopolyol is commercially available as a mixture with polyglyceryl-4isostearate (and) hexyl laurate and is sold under the tradename ABIL®WE-09 (available from Goldschmidt). Cetyl dimethicone copolyol is alsocommercially available as a mixture with hexyl laurate (and)polyglyceryl-3 oleate (and) cetyl dimethicone and is sold under thetradename ABIL® WS-08 (also available from Goldschmidt). Othernonlimiting examples of dimethicone copolyols also include lauryldimethicone copolyol, dimethicone copolyol acetate, diemethiconecopolyol adipate, dimethicone copolyolamine, dimethicone copolyolbehenate, dimethicone copolyol butyl ether, dimethicone copolyol hydroxystearate, dimethicone copolyol isostearate, dimethicone copolyollaurate, dimethicone copolyol methyl ether, dimethicone copolyolphosphate, and dimethicone copolyol stearate.

Dimethicone copolyol emulsifiers useful herein are described, forexample, in U.S. Pat. No. 4,960,764, European Patent No. EP 330,369,Among the non-silicone-containing emulsifiers useful herein are variousnon-ionic and anionic emulsifying agents such as sugar esters andpolyesters, alkoxylated sugar esters and polyesters, C1-C30 fatty acidesters of C1-C30 fatty alcohols, alkoxylated derivatives of C1-C30 fattyacid esters of C1-C30 fatty alcohols, alkoxylated ethers of C1-C30 fattyalcohols, polyglyceryl esters of C1-C30 fatty acids, C1-C30 esters ofpolyols, C1-C30 ethers of polyols, alkyl phosphates, polyoxyalkylenefatty ether phosphates, fatty acid amides, acyl lactylates, soaps, andmixtures thereof. Other suitable emulsifiers are described, for example,in McCutcheon's, Detergents and Emulsifiers, North American Edition(1986), published by Allured Publishing Corporation; U.S. Pat. No.5,011,681; U.S. Pat. No. 4,421,769; and U.S. Pat. No. 3,755,560

Nonlimiting examples of these non-silicon-containing emulsifiersinclude: polyethylene glycol 20 sorbitan monolaurate (Polysorbate 20),polyethylene glycol 5 soya sterol, Steareth-20, Ceteareth-20, PPG-2methyl glucose ether distearate, Ceteth-10, Polysorbate 80, cetylphosphate, potassium cetyl phosphate, diethanolamine cetyl phosphate,Polysorbate 60, glyceryl stearate, PEG-100 stearate, polyoxyethylene 20sorbitan trioleate (Polysorbate 85), sorbitan monolaurate,polyoxyethylene 4 lauryl ether sodium stearate, polyglyceryl-4isostearate, hexyl laurate, steareth-20, ceteareth-20, PPG-2 methylglucose ether distearate, ceteth-10, diethanolamine cetyl phosphate,glyceryl stearate, PEG-100 stearate, and mixtures thereof.

d) Silicone Elastomer

The compositions of the present invention also include from about 0.1%to about 30%, by weight of the composition, of a silicone elastomercomponent. Preferably, the composition includes from about 1% to about30%, more preferably from about 2% to about 20%, by weight of thecomposition, of the silicone elastomer component.

Suitable for use herein are silicone elastomers, which can beemulsifying or non-emulsifying crosslinked siloxane elastomers ormixtures thereof. No specific restriction exists as to the type ofcurable organopolysiloxane composition that can serve as startingmaterial for the crosslinked organopolysiloxane elastomer. Examples inthis respect are addition reaction-curing organopolysiloxanecompositions which cure under platinum metal catalysis by the additionreaction between SiH-containing diorganopolysiloxane andorganopolysiloxane having silicon-bonded vinyl groups;condensation-curing organopolysiloxane compositions which cure in thepresence of an organotin compound by a dehydrogenation reaction betweenhydroxyl-terminated diorganopolysiloxane and SiH-containingdiorganopolysiloxane and condensation-curing organopolysiloxanecompositions which cure in the presence of an organotin compound or atitanate ester.

Addition reaction-curing organopolysiloxane compositions are preferredfor their rapid curing rates and excellent uniformity of curing. Aparticularly preferred addition reaction-curing organopolysiloxanecomposition is prepared from: a) an organopolysiloxane having at least 2lower alkenyl groups in each molecule; b) an organopolysiloxane havingat least 2 silicon-bonded hydrogen atoms in each molecule; and c) aplatinum-type catalyst.

The compositions of the present invention may include an emulsifyingcrosslinked organopolysiloxane elastomer, a non-emulsifying crosslinkedorganopolysiloxane elastomer, or a mixture thereof. The term“non-emulsifying,” as used herein, defines crosslinkedorganopolysiloxane elastomers from which polyoxyalkylene units areabsent. The term “emulsifying,” as used herein, means crosslinkedorganopolysiloxane elastomers having at least one polyoxyalkylene (e.g.,polyoxyethylene or polyoxypropylene) unit. Preferred emulsifyingelastomers herein include polyoxyalkylene modified elastomers formedfrom divinyl compounds, particularly siloxane polymers with at least twofree vinyl groups, reacting with Si—H linkages on a polysiloxanebackbone. Preferably, the elastomers are dimethyl polysiloxanescrosslinked by Si—H sites on a molecularly spherical MQ resin.Emulsifying crosslinked organopolysiloxane elastomers can notably bechosen from the crosslinked polymers described in U.S. Pat. Nos.5,412,004, 5,837,793, and 5,811,487. In addition, an emulsifyingelastomer comprised of dimethicone copolyol crosspolymer (and)dimethicone is available from Shin Etsu under the tradename KSG-21.

Advantageously, the non-emulsifying elastomers are dimethicone/vinyldimethicone crosspolymers. Such dimethicone/vinyl dimethiconecrosspolymers are supplied by a variety of suppliers including DowCorning (DC 9040 and DC 9041), General Electric (SFE 839), Shin Etsu(KSG-15, 16, 18 [dimethicone/phenyl vinyl dimethicone crosspolymer]),and Grant Industries (GRANSIL™ line of elastomers). Cross-linkedorganopolysiloxane elastomers useful in the present invention andprocesses for making them are further described in U.S. Pat. No.4,970,252, U.S. Pat. No. 5,760,116 and U.S. Pat. No. 5,654,362.

Commercially available elastomers preferred for use herein are DowCorning's 9040 silicone elastomer blend, Shin Etsu's KSG-21, andmixtures thereof.

e) Carrier for Silicone Elastomer

The topical compositions of the present invention may include from about1% to about 80%, by weight of the composition, of a suitable carrier forthe for the crosslinked organopolysiloxane elastomer component describedabove. The carrier, when combined with the cross-linkedorganopolysiloxane elastomer particles of the present invention, servesto suspend and swell the elastomer particles to provide an elastic,gel-like network or matrix. The carrier for the cross-linked siloxaneelastomer is liquid under ambient conditions, and preferably has a lowviscosity to provide for improved spreading on the skin.

Concentrations of the carrier in the cosmetic compositions of thepresent invention will vary primarily with the type and amount ofcarrier and the cross-linked siloxane elastomer employed. Preferredconcentrations of the carrier are from about 5% to about 50%, morepreferably from about 5% to about 40%, by weight of the composition.

The carrier for the cross-linked siloxane elastomer includes one or moreliquid carriers suitable for topical application to human skin. Theseliquid carriers may be organic, silicone-containing orfluorine-containing, volatile or non-volatile, polar or non-polar,provided that the liquid carrier forms a solution or other homogenousliquid or liquid dispersion with the selected cross-linked siloxaneelastomer at the selected siloxane elastomer concentration at atemperature of from about 28° C. to about 250° C., preferably from about28° C. to about 100° C., preferably from about 28° C. to about 78° C.The term “volatile” as used herein refers to all materials that are not“non-volatile” as previously defined herein. The phrase “relativelypolar” as used herein means more polar than another material in terms ofsolubility parameter; i.e., the higher the solubility parameter the morepolar the liquid. The term “non-polar” typically means that the materialhas a solubility parameter below about 6.5 (cal/cm3>)05.

f) Non-Polar, Volatile Oils

The composition of the present invention may include non-polar, volatileoils. The non-polar, volatile oil tends to impart highly desirableaesthetic properties to the compositions of the present invention.Consequently, the non-polar, volatile oils are preferably utilized at afairly high level. Non-polar, volatile oils particularly useful in thepresent invention are silicone oils; hydrocarbons; and mixtures thereof.Such non-polar, volatile oils are disclosed, for example, in Cosmetics,Science, and Technology, Vol. 1, 27-104 edited by Balsam and Sagarin,1972. Examples of preferred non-polar, volatile hydrocarbons includepolydecanes such as isododecane and isodecane (e.g., Permethyl-99A whichis available from Presperse Inc.) and the C7-C8 through C12-C15isoparaffins (such as the Isopar Series available from Exxon Chemicals).Linear volatile silicones generally have a viscosity of less than about5 centistokes at 25° C., whereas the cyclic silicones have viscositiesof less than about 10 centistokes at 25° C. Highly preferred examples ofvolatile silicone oils include cyclomethicones of varying viscosities,e.g., Dow Corning 200, Dow Corning 244, Dow Corning 245, Dow Corning344, and Dow Corning 345, (commercially available from Dow CorningCorp.); SF-1204 and SF-1202 Silicone Fluids (commercially available fromG.E. Silicones), GE 7207 and 7158 (commercially available from GeneralElectric Co.); and SWS-03314 (commercially available from SWS SiliconesCorp.).

g) Relatively Polar, Non-Volatile Oils

The composition of the present invention may include relatively polar,non-volatile oils. The non-volatile oil is “relatively polar” ascompared to the non-polar, volatile oil discussed above. Therefore, thenon-volatile co-carrier is more polar (i.e., has a higher solubilityparameter) than at least one of the non-polar, volatile oils. Relativelypolar, non-volatile oils potentially useful in the present invention aredisclosed, for example, in Cosmetics, Science, and Technology, Vol. 1,27-104 edited by Balsam and Sagarin, 1972; U.S. Pat. Nos. 4,202,879 and4,816,261. Relatively polar, non-volatile oils useful in the presentinvention are preferably selected from silicone oils; hydrocarbon oils;fatty alcohols; fatty acids; esters of mono and dibasic carboxylic acidswith mono and polyhydric alcohols; polyoxyethylenes; polyoxypropylenes;mixtures of polyoxyethylene and polyoxypropylene ethers of fattyalcohols; and mixtures thereof.

h) Non-Polar, Non-Volatile Oils

In addition to the liquids discussed above, the carrier for thecross-linked siloxane elastomer may optionally include non-volatile,non-polar oils. Typical non-volatile, non-polar emollients aredisclosed, for example, in Cosmetics, Science, and Technology, Vol. 1,27-104 edited by Balsam and Sagarin, 1972; U.S. Pat. Nos. 4,202,879 and4,816,261. The non-volatile oils useful in the present invention areessentially non-volatile polysiloxanes, paraffinic hydrocarbon oils, andmixtures thereof.

2) Oil-in-Water Emulsions

Other preferred topical carriers include oil-in-water emulsions, havinga continuous aqueous phase and a hydrophobic, water-insoluble phase(“oil phase”) dispersed therein. The “oil phase” can contain oil,silicone or mixtures thereof, and includes but is not limited to theoils and silicones described above in the section on water-in-oilemulsions. The distinction of whether the emulsion is characterized asan oil-in-water or silicone-in-water emulsions is a function of whetherthe oil phase is composed of primarily oil or silicone. The water phaseof these emulsions consists primarily of water, but can also containvarious other ingredients such as those water phase ingredients listedin the above section on water-in-oil emulsion. The preferredoil-in-water emulsions comprises from about 25% to about 98%, preferablyfrom about 65% to about 95%, more preferably from about 70% to about 90%water by weight of the total composition.

In addition to a continuous water phase and dispersed oil or siliconephase, these oil-in-water compositions also comprise an emulsifier tostabilize the emulsion. Emulsifiers useful herein are well known in theart, and include nonionic, anionic, cationic, and amphotericemulsifiers. Non-limiting examples of emulsifiers useful in theoil-in-water emulsions of this invention are given in McCutcheon's,Detergents and Emulsifiers, North American Edition (1986), U.S. Pat. No.5,011,681, U.S. Pat. No. 4,421,769 and U.S. Pat. No. 3,755,560. Examplesof suitable oil-in-water emulsion carriers are described in U.S. Pat.No. 5,073,371 and U.S. Pat. No. 5,073,372. An especially preferredoil-in-water emulsion, containing a structuring agent, hydrophilicsurfactant and water, is described in detail hereinafter.

a) Structuring Agent

A preferred oil-in-water emulsion contains a structuring agent to assistin the formation of a liquid crystalline gel network structure. Withoutbeing limited by theory, it is believed that the structuring agentassists in providing rheological characteristics to the compositionwhich contribute to the stability of the composition. The structuringagent may also function as an emulsifier or surfactant. Preferredcompositions of this invention contain from about 0.5% to about 20%,more preferably from about 1% to about 10%, even more preferably fromabout 1% to about 5%, by weight of the composition, of a structuringagent.

The preferred structuring agents of the present invention includestearic acid, palmitic acid, stearyl alcohol, cetyl alcohol, behenylalcohol, the polyethylene glycol ether of stearyl alcohol having anaverage of about 1 to about 21 ethylene oxide units, the polyethyleneglycol ether of cetyl alcohol having an average of about 1 to about 5ethylene oxide units, and mixtures thereof. More preferred structuringagents of the present invention are selected from stearyl alcohol, cetylalcohol, behenyl alcohol, the polyethylene glycol ether of stearylalcohol having an average of about 2 ethylene oxide units (steareth-2),the polyethylene glycol ether of stearyl alcohol having an average ofabout 21 ethylene oxide units (steareth-21), the polyethylene glycolether of cetyl alcohol having an average of about 2 ethylene oxideunits, and mixtures thereof. Even more preferred structuring agents areselected from stearic acid, palmitic acid, stearyl alcohol, cetylalcohol, behenyl alcohol, steareth-2, steareth-21, and mixtures thereof.

b) Hydrophilic Surfactant

The preferred oil-in-water emulsions contain from about 0.05% to about10%, preferably from about 1% to about 6%, and more preferably fromabout 1% to about 3% of at least one hydrophilic surfactant which candisperse the hydrophobic materials in the water phase (percentages byweight of the topical carrier). The surfactant, at a minimum, must behydrophilic enough to disperse in water.

Preferred hydrophilic surfactants are selected from nonionicsurfactants. Among the nonionic surfactants that are useful herein arethose that can be broadly defined as condensation products of long chainalcohols, e.g. C8-30 alcohols, with sugar or starch polymers, i.e.,glycosides. These compounds can be represented by the formula (S)n-O—Rwherein S is a sugar moiety such as glucose, fructose, mannose, andgalactose; n is an integer of from about 1 to about 1000, and R is aC8-30 alkyl group. Examples of long chain alcohols from which the alkylgroup can be derived include decyl alcohol, cetyl alcohol, stearylalcohol, lauryl alcohol, myristyl alcohol, oleyl alcohol, and the like.Preferred examples of these surfactants include those wherein S is aglucose moiety, R is a C8-20 alkyl group, and n is an integer of fromabout 1 to about 9. Commercially available examples of these surfactantsinclude decyl polyglucoside (available as APG 325 CS from Henkel) andlauryl polyglucoside (available as APG 600 CS and 625 CS from Henkel).

Other useful nonionic surfactants include the condensation products ofalkylene oxides with fatty acids (i.e. alkylene oxide esters of fattyacids), the condensation products of alkylene oxides with 2 moles offatty acids (i.e. alkylene oxide diesters of fatty acids), thecondensation products of alkylene oxides with fatty alcohols (i.e.alkylene oxide ethers of fatty alcohols), the condensation products ofalkylene oxides with both fatty acids and fatty alcohols [i.e. whereinthe polyalkylene oxide portion is esterified on one end with a fattyacid and etherified (i.e. connected via an ether linkage) on the otherend with a fatty alcohol]. Nonlimiting examples of these alkylene oxidederived nonionic surfactants include ceteth-6, ceteth-10, ceteth-12,ceteareth-6, ceteareth-10, ceteareth-12, steareth-6, steareth-10,steareth-12, steareth-21, PEG-6 stearate, PEG-10 stearate, PEG-100stearate, PEG-12 stearate, PEG-20 glyceryl stearate, PEG-80 glyceryltallowate, PEG-10 glyceryl stearate, PEG-30 glyceryl cocoate, PEG-80glyceryl cocoate, PEG-200 glyceryl tallowate, PEG-8 dilaurate, PEG-10distearate, and mixtures thereof.

Still other useful nonionic surfactants include polyhydroxy fatty acidamide surfactants, An especially preferred surfactant corresponding tothe above structure is coconut alkyl N-methyl glucoside amide. Processesfor making compositions containing polyhydroxy fatty acid amides aredisclosed, for example, U.S. Pat. No. 2,965,576; U.S. Pat. No.2,703,798, and U.S. Pat. No. 1,985,424.

Preferred among the nonionic surfactants are those selected from thegroup consisting of steareth-21, ceteareth-20, ceteareth-12, sucrosecocoate, steareth-100, PEG-100 stearate, and mixtures thereof. Othernonionic surfactants suitable for use herein include sugar esters andpolyesters, alkoxylated sugar esters and polyesters, C1-C30 fatty acidesters of C1-C30 fatty alcohols, alkoxylated derivatives of C1-C30 fattyacid esters of C1-C30 fatty alcohols, alkoxylated ethers of C1-C30 fattyalcohols, polyglyceryl esters of C1-C30 fatty acids, C1-C30 esters ofpolyols, C1-C30 ethers of polyols, alkyl phosphates, polyoxyalkylenefatty ether phosphates, fatty acid amides, acyl lactylates, and mixturesthereof. Nonlimiting examples of these emulsifiers include: polyethyleneglycol 20 sorbitan monolaurate (Polysorbate 20), polyethylene glycol 5soya sterol, Steareth-20, Ceteareth-20, PPG-2 methyl glucose etherdistearate, Ceteth-10, Polysorbate 80, cetyl phosphate, potassium cetylphosphate, diethanolamine cetyl phosphate, Polysorbate 60, glycerylstearate, polyoxyethylene 20 sorbitan trioleate (Polysorbate 85),sorbitan monolaurate, polyoxyethylene 4 lauryl ether sodium stearate,polyglyceryl-4 isostearate, hexyl laurate, PPG-2 methyl glucose etherdistearate, PEG-100 stearate, and mixtures thereof.

Another group of non-ionic surfactants useful herein are fatty acidester blends based on a mixture of sorbitan or sorbitol fatty acid esterand sucrose fatty acid ester, the fatty acid in each instance beingpreferably C8-C24, more preferably C10-C20. The preferred fatty acidester emulsifier is a blend of sorbitan or sorbitol C16-C20 fatty acidester with sucrose C10-C16 fatty acid ester, especially sorbitanstearate and sucrose cocoate. This is commercially available from ICIunder the trade name Arlatone 2121.

Other suitable surfactants useful herein include a wide variety ofcationic, anionic, zwitterionic, and amphoteric surfactants such as areknown in the art and discussed more fully below. The hydrophilicsurfactants useful herein can contain a single surfactant, or anycombination of suitable surfactants. The exact surfactant (orsurfactants) chosen will depend upon the pH of the composition and theother components present.

Also useful herein are cationic surfactants, especially dialkylquaternary ammonium compounds, examples of which are described in U.S.Pat. No. 5,151,209; U.S. Pat. No. 5,151,210; U.S. Pat. No. 5,120,532;U.S. Pat. No. 4,387,090; U.S. Pat. No. 3,155,591; U.S. Pat. No.3,929,678; U.S. Pat. No. 3,959,461; McCutcheon's, Detergents &Emulsifiers, (North American edition 1979) M.C. Publishing Co.; andSchwartz, et al., Surface Active Agents, Their Chemistry and Technology,New York: Interscience Publishers, 1949.

Nonlimiting examples of these cationic emulsifiers includestearamidopropyl PG-dimonium chloride phosphate, behenamidopropyl PGdimonium chloride, stearamidopropyl ethyldimonium ethosulfate,stearamidopropyl dimethyl(myristyl acetate)ammonium chloride,stearamidopropyl dimethyl cetearyl ammonium tosylate, stearamidopropyldimethyl ammonium chloride, stearamidopropyl dimethyl ammonium lactate,and mixtures thereof. Especially preferred is behenamidopropyl PGdimonium chloride.

Nonlimiting examples of quaternary ammonium salt cationic surfactantsinclude those selected from cetyl ammonium chloride, cetyl ammoniumbromide, lauryl ammonium chloride, lauryl ammonium bromide, stearylammonium chloride, stearyl ammonium bromide, cetyl dimethyl ammoniumchloride, cetyl dimethyl ammonium bromide, lauryl dimethyl ammoniumchloride, lauryl dimethyl ammonium bromide, stearyl dimethyl ammoniumchloride, stearyl dimethyl ammonium bromide, cetyl trimethyl ammoniumchloride, cetyl trimethyl ammonium bromide, lauryl trimethyl ammoniumchloride, lauryl trimethyl ammonium bromide, stearyl trimethyl ammoniumchloride, stearyl trimethyl ammonium bromide, lauryl dimethyl ammoniumchloride, stearyl dimethyl cetyl ditallow dimethyl ammonium chloride,dicetyl ammonium chloride, dicetyl ammonium bromide, dilauryl ammoniumchloride, dilauryl ammonium bromide, distearyl ammonium chloride,distearyl ammonium bromide, dicetyl methyl ammonium chloride, dicetylmethyl ammonium bromide, dilauryl methyl ammonium chloride, dilaurylmethyl ammonium bromide, distearyl methyl ammonium chloride, distearylmethyl ammonium bromide, and mixtures thereof. Additional quaternaryammonium salts include those wherein the C12 to C30 alkyl carbon chainis derived from a tallow fatty acid or from a coconut fatty acid. Theterm “tallow” refers to an alkyl group derived from tallow fatty acids(usually hydrogenated tallow fatty acids), which generally have mixturesof alkyl chains in the C16 to C18 range. The term “coconut” refers to analkyl group derived from a coconut fatty acid, which generally havemixtures of alkyl chains in the C12 to C14 range. Examples of quaternaryammonium salts derived from these tallow and coconut sources includeditallow dimethyl ammonium chloride, ditallow dimethyl ammonium methylsulfate, di(hydrogenated tallow) dimethyl ammonium chloride,di(hydrogenated tallow) dimethyl ammonium acetate, ditallow dipropylammonium phosphate, ditallow dimethyl ammonium nitrate,di(coconutalkyl)dimethyl ammonium chloride, di(coconutalkyl)dimethylammonium bromide, tallow ammonium chloride, coconut ammonium chloride,and mixtures thereof. An example of a quaternary ammonium compoundhaving an alkyl group with an ester linkage is ditallowyl oxyethyldimethyl ammonium chloride.

More preferred cationic surfactants are those selected frombehenamidopropyl PG dimonium chloride, dilauryl dimethyl ammoniumchloride, distearyl dimethyl ammonium chloride, dimyristyl dimethylammonium chloride, dipalmityl dimethyl ammonium chloride, distearyldimethyl ammonium chloride, stearamidopropyl PG-dimonium chloridephosphate, stearamidopropyl ethyldiammonium ethosulfate,stearamidopropyl dimethyl(myristyl acetate)ammonium chloride,stearamidopropyl dimethyl cetearyl ammonium tosylate, stearamidopropyldimethyl ammonium chloride, stearamidopropyl dimethyl ammonium lactate,and mixtures thereof.

Still more preferred cationic surfactants are those selected frombehenamidopropyl PG dimonium chloride, dilauryl dimethyl ammoniumchloride, distearyl dimethyl ammonium chloride, dimyristyl dimethylammonium chloride, dipalmityl dimethyl ammonium chloride, and mixturesthereof.

A preferred combination of cationic surfactant and structuring agent isbehenamidopropyl PG dimonium chloride and/or behenyl alcohol, whereinthe ratio is preferably optimized to maintained to enhance physical andchemical stability, especially when such a combination contains ionicand/or highly polar solvents.

A wide variety of anionic surfactants can also be useful herein.Nonlimiting examples of anionic surfactants include the alkoylisethionates, and the alkyl and alkyl ether sulfates. The reactionproducts of fatty acids esterified with isethianonic acid andneutralized, i.e. the alkoyl isethionates typically have the formulaRCO—OCH2CH2SO3M wherein R is alkyl or alkenyl of from about 10 to about30 carbon atoms, and M is a water-soluble cation such as ammonium,sodium, potassium and triethanolamine. For example, the fatty acids arederivated from coconut or palm kernel oil. Nonlimiting examples of theseisethionates include those alkoyl isethionates selected from ammoniumcocoyl isethionate, sodium cocoyl isethionate, sodium lauroylisethionate, sodium stearoyl isethionate, and mixtures thereof. Alsosuitable are salts of fatty acids, amids of methyl taurides. Othersimilar anionic surfactants are described in U.S. Pat. Nos. 2,486,921;2,486,922 and 2,396,278.

The alkyl and alkyl ether sulfates typically have the respectiveformulae ROSO3M and RO(C2H40)xSO3M, wherein R is alkyl or alkenyl offrom about 10 to about 30 carbon atoms, x is from about 1 to about 10,and M is a water-soluble cation such as ammonium, alkanolamines such astriethanolamine, monovalent metals, such as sodium and potassium, andpolyvalent metal cations such as magnesium and calcium. Preferably, Rhas from about 8 to about 18 carbon atoms, more preferably from about 10to about 16 carbon atoms, even more preferably from about 12 to about 14carbon atoms, in both the alkyl and alkyl ether sulfates. The alkylether sulfates are typically made as condensation products of ethyleneoxide and monohydric alcohols having from about 8 to about 24 carbonatoms. The alcohols can be synthetic or they can be derived from fats,e.g., coconut oil, palm kernel oil, tallow. Lauryl alcohol and straightchain alcohols derived from coconut oil or palm kernel oil arepreferred. Such alcohols are reacted with between about 0 and about 10,preferably from about 2 to about 5, more preferably about 3, molarproportions of ethylene oxide, and the resulting mixture of molecularspecies having, for example, an average of 3 moles of ethylene oxide permole of alcohol, is sulfated and neutralized

Another suitable class of anionic surfactants are the water-solublesalts of the organic, sulfuric acid reaction products of the generalformula:R1-SO3-M

wherein R1 is chosen from the group including a straight or branchedchain, saturated aliphatic hydrocarbon radical having from about 8 toabout 24, preferably about 10 to about 16, carbon atoms; and M is acation described hereinbefore. Still other anionic synthetic surfactantsinclude the class designated as succinamates, olefin sulfonates havingabout 12 to about 24 carbon atoms, and β-alkyloxy alkane sulfonates.Examples of these materials are sodium lauryl sulfate and ammoniumlauryl sulfate. Other anionic surfactants suitable for use in thecompositions are the succinnates, examples of which include disodiumN-octadecylsulfosuccinnate; disodium lauryl sulfosuccinate; diammoniumlauryl sulfosuccinate; tetrasodiumN-(1,2-dicarboxyethyl)-N-octadecylsulfosuccinnate; diamyl ester ofsodium sulfosuccinic acid; dihexyl ester of sodium sulfosuccinic acid;and dioctyl esters of sodium sulfosuccinic acid. Other suitable anionicsurfactants include olefin sulfonates having about 10 to about 24 carbonatoms. In addition to the true alkene sulfonates and a proportion ofhydroxy-alkanesulfonates, the olefin sulfonates can contain minoramounts of other materials, such as alkene disulfonates depending uponthe reaction conditions, proportion of reactants, the nature of thestarting olefins and impurities in the olefin stock and side reactionsduring the sulfonation process. A non limiting example of such analpha-olefin sulfonate mixture is described in U.S. Pat. No. 3,332,880.

Another class of anionic surfactants suitable for use in thecompositions is the beta-alkyloxy alkane sulfonate class. Thesesurfactants conform to the formula

where R1 is a straight chain alkyl group having from about 6 to about 20carbon atoms, R2 is a lower alkyl group having from about 1 to about 3carbon atoms, preferably 1 carbon atom, and M is a water-soluble cationas described hereinbefore. Other anionic materials useful herein aresoaps (i.e. alkali metal salts, e.g., sodium or potassium salts) offatty acids, typically having from about 8 to about 24 carbon atoms,preferably from about 10 to about 20 carbon atoms. The fatty acids usedin making the soaps can be obtained from natural sources such as, forinstance, plant or animal-derived glycerides (e.g., palm oil, coconutoil, soybean oil, castor oil, tallow, lard, etc.) The fatty acids canalso be synthetically prepared. Soaps are described in more detail inU.S. Pat. No. 4,557,853.

Amphoteric and zwitterionic surfactants are also useful herein. Examplesof amphoteric and zwitterionic surfactants which can be used in thecompositions of the present invention are those which are broadlydescribed as derivatives of aliphatic secondary and tertiary amines inwhich the aliphatic radical can be straight or branched chain andwherein one of the aliphatic substituents contains from about 8 to about22 carbon atoms (preferably C8-C18) and one contains an anionic watersolubilizing group, e.g., carboxy, sulfonate, sulfate, phosphate, orphosphonate. Examples are alkyl imino acetates, and iminodialkanoatesand aminoalkanoates of the formulas RN[CH2)mCO2M]2 and RNH(CH2)mCO2Mwherein m is from 1 to 4, R is a C8-C22 alkyl or alkenyl, and M is H,alkali metal, alkaline earth metal ammonium, or alkanolammonium.Preferred amphoteric surfactants for use in the present inventioninclude cocoamphoacetate, cocoamphodiacetate, lauroamphoacetate,lauroamphodiacetate, and mixtures thereof. Also included areimidazolinium and ammonium derivatives. Specific examples of suitableamphoteric surfactants include sodium 3-dodecyl-aminopropionate, sodium3-dodecylaminopropane sulfonate, N-alkyltaurines such as the oneprepared by reacting dodecylamine with sodium isethionate according tothe teaching of U.S. Pat. No. 2,658,072; N-higher alkyl aspartic acidssuch as those produced according to the teaching of U.S. Pat. No.2,438,091; and the products sold under the trade name “Miranol” anddescribed in U.S. Pat. No. 2,528,378. Other examples of usefulamphoterics include phosphates, such as coamidopropyl PG-dimoniumchloride phosphate (commercially available as Monaquat PTC, from MonaCorp.).

Zwitterionic surfactants suitable for use in the composition are wellknown in the art, and include those surfactants broadly described asderivatives of aliphatic quaternary ammonium, phosphonium, and sulfoniumcompounds, in which the aliphatic radicals can be straight or branchedchain, and wherein one of the aliphatic substituents contains from about8 to about 18 carbon atoms and one contains an anionic group such ascarboxy, sulfonate, sulfate, phosphate or phosphonate. Zwitterionicssuch as betaines are preferred. Examples of betaines include the higheralkyl betaines, such as coco dimethyl carboxymethyl betaine, lauryldimethyl carboxymethyl betaine, lauryl dimethyl alphacarboxyethylbetaine, cetyl dimethyl carboxymethyl betaine, cetyl dimethyl betaine(available as Lonzaine 16SP from Lonza Corp.), laurylbis-(2-hydroxyethyl)carboxymethyl betaine, stearylbis-(2-hydroxypropyl)carboxymethyl betaine, oleyl dimethylgamma-carboxypropyl betaine, laurylbis-(2-hydroxypropyl)alpha-carboxyethyl betaine, coco dimethylsulfopropyl betaine, stearyl dimethyl sulfopropyl betaine, lauryldimethyl sulfoethyl betaine, lauryl bis-(2-hydroxyethyl)sulfopropylbetaine, and amidobetaines and amidosulfobetaines (wherein theRCONH(CH2)3 radical is attached to the nitrogen atom of the betaine),oleyl betaine (available as amphoteric Velvetex OLB-50 from Henkel), andcocamidopropyl betaine (available as Velvetex BK-35 and BA-35 fromHenkel).

Other useful amphoteric and zwitterionic surfactants include thesultaines and hydroxysultaines such as cocamidopropyl hydroxysultaine(available as Mirataine CBS from Rhone-Poulenc), and the alkanoylsarcosinates corresponding to the formula RCON(CH3)CH2CH2CO2M wherein Ris alkyl or alkenyl of about 10 to about 20 carbon atoms, and M is awater-soluble cation such as ammonium, sodium, potassium andtrialkanolamine (e.g., triethanolamine), a preferred example of which issodium lauroyl sarcosinate.

c) Water Emollient

The preferred oil-in-water emulsion contains from about 25% to about98%, preferably from about 65% to about 95%, more preferably from about70% to about 90% water by weight of the topical carrier.

The hydrophobic phase is dispersed in the continuous aqueous phase. Thehydrophobic phase may contain water insoluble or partially solublematerials such as are known in the art, including but not limited to thesilicones described herein in reference to silicone-in-water emulsions,and other oils and lipids such as described above in reference toemulsions.

The topical compositions of the subject invention, including but notlimited to lotions and creams, may contain a dermatologically acceptableemollient. Such compositions preferably contain from about 1% to about50% of the emollient. As used herein, “emollient” refers to a materialuseful for the prevention or relief of dryness, as well as for theprotection of the skin. A wide variety of suitable emollients is knownand may be used herein. Sagarin, Cosmetics, Science and Technology, 2ndEdition, Vol. 1, pp. 32-43 (1972) contains numerous examples ofmaterials suitable as an emollient. A preferred emollient is glycerin.Glycerin is preferably used in an amount of from or about 0.001 to orabout 30%, more preferably from or about 0.01 to or about 20%, stillmore preferably from or about 0.1 to or about 10%, e.g., 5%.

Lotions and creams according to the present invention generally containa solution carrier system and one or more emollients. Lotions and creamstypically contain from about 1% to about 50%, preferably from about 1%to about 20%, of emollient; from about 50% to about 90%, preferably fromabout 60% to about 80%, water; the actives and the additional skin careactive (or actives) in the above described amounts. Creams are generallythicker than lotions due to higher levels of emollients or higher levelsof thickeners.

Ointments of the present invention may contain a simple carrier base ofanimal or vegetable oils or semi-solid hydrocarbons (oleaginous);absorption ointment bases which absorb water to form emulsions; or watersoluble carriers, e.g., a water soluble solution carrier. Ointments mayfurther contain a thickening agent, such as described in Sagarin,Cosmetics, Science and Technology, 2nd Edition, Vol. 1, pp. 72-73(1972), and/or an emollient. For example, an ointment may contain fromabout 2% to about 10% of an emollient; from about 0.1% to about 2% of athickening agent as well as the active ingredient(s) and the additionalingredient(s) in the above described amounts.

Compositions of this invention useful for cleansing (“cleansers”) can beformulated with a suitable carrier, e.g., as described above, andpreferably comprise from about 1% to about 90%, more preferably fromabout 5% to about 10%, of a dermatologically acceptable surfactant. Thesurfactant is suitably selected from anionic, nonionic, zwitterionic,amphoteric and ampholytic surfactants, as well as mixtures of thesesurfactants. Such surfactants are well known to those skilled in thedetergency art. Nonlimiting examples of possible surfactants includeisoceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyltaurate, and sodium lauryl sulfate. See U.S. Pat. No. 4,800,197, forexemplary surfactants useful herein. Examples of a broad variety ofadditional surfactants useful herein are described in McCutcheon'sDetergents and Emulsifiers, North American Edition (1986), published byAllured Publishing Corporation. The cleansing compositions canoptionally contain, at their art-established levels, other materialswhich are conventionally used in cleansing compositions.

As used herein, the term “foundation” refers to a liquid, semi-liquid,semi-solid, or solid skin cosmetic which includes, but is not limited tolotions, creams, gels, pastes, cakes, and the like. Typically thefoundation is used over a large area of the skin, such as over the face,to provide a particular look. Foundations are typically used to providean adherent base for color cosmetics such as rouge, blusher, powder andthe like, and tend to hide skin imperfections and impart a smooth, evenappearance to the skin. Foundations of the present invention include adermatologically acceptable carrier and may include conventionalingredients such as oils, colorants, pigments, emollients, fragrances,waxes, stabilizers, and the like. Exemplary carriers and such otheringredients which are suitable for use herein are described, for examplein PCT Application WO 96/33689, and U.K. Patent GB 2274585.

B. Orally Acceptable Carrier

The compositions of the present invention can also comprise an orallyacceptable carrier if they are to be ingested. Any suitable orallyingestible carrier or carrier form, as known in the art or otherwise,can be used. Non-limiting examples of oral personal care compositionscan include, but are not limited to, tablets, pills, capsules, drinks,beverages, syrups, granules, powders, vitamins, supplements, healthbars, candies, chews, and drops.

C. Injectible Liquid

The compositions of the present invention can also comprise a liquidthat is acceptable for injection in and/or under the skin if thecomposition is to be injected. Any suitable acceptable liquid as knownin the art or otherwise can be used.

III. COMPOSITION PREPARATION

The compositions of the present invention are generally prepared byconventional methods such as are known in the art of making topical andoral compositions and compositions for injection. Such methods cantypically be conducted in one or more steps, with or without heating,cooling, and the like.

The physical form of the compositions according to the invention is notimportant: they may be in any galenic form such creams, lotions, milk orcream ointments, gels, emulsions, dispersions, solutions, suspensions,cleansers, foundations, anhydrous preparations (sticks, in particularlipbalm, body and bath oils), shower and bath gels, shampoos and scalptreatment lotions, cream or lotion for care of skin or hair, make-upremoving lotions or creams, sun-screen lotions, milks or creams,artificial suntan lotions, creams or milks, pre-shave, shave oraftershave creams, foams, gels or lotions, make-up, lipsticks, mascarasor nail varnishes, skin “essences,” serums, adhesive or absorbentmaterials, transdermal patches, or powders, emollient lotion, milk orcream, sprays, oils for the body and the bath, foundation tint bases,pomade, emulsion, colloid, compact or solid suspension, pencil,sprayable or brossable formulation, blush, red, eyeliner, lipliner, lipgloss, facial or body powder, styling foams or gels, nail conditioner,lip balms, skin conditioners, moisturizers, hair sprays, soaps, bodyexfoliants, astringents, depilatories and permanent waving solutions,antidandruff formulations, anti-sweat and antiperspirant compositions,nose sprays and so on. These compositions can also be presented in theform of lipsticks intended to apply colour or to protect the lips fromcracking, or of make-up products for the eyes or tints and tint basesfor the face. Compositions in accordance with the invention includecosmetics, personal care products and pharmaceutical preparations. Thepresent invention may also be applied on animal skin and/or appendages.One can also consider a composition in the shape of foam or in the formof compositions for aerosol also including a propellant agent underpressure.

Cosmetic compositions according to the invention may also be fororodental use, for example, toothpaste. In that case, the compositionsmay contain the usual adjuvants and additives for compositions for oraluse and, in particular, surfactants, thickening agents, moisturizingagents, polishing agents such as silica, various active substances suchas fluorides, particularly sodium fluoride, and, possibly, sweeteningagents such as saccharin sodium.

Oridonin or the combination of oridonin and darutigenol or thecombination of oridonin and darutoside according to the presentinvention may be in the form of solution, dispersion, emulsion, paste,or powder, individually or as a premix or in vehicles individually or asa premix in vectors such as macro-, micro-, or nanocapsules, macro-,micro- or, nanospheres, liposomes, oleosomes or chylomicrons, macro-,micro-, or nanoparticles or macro-, micro or nanosponges, micro or nanoemulsions or adsorbed on organic polymer powders, talcs, bentonites, orother inorganic or organic supports.

Oridonin or the combination of oridonin and darutigenol or thecombination of oridonin and darutoside according to the presentinvention may be used in any form whatsoever, in a form bound to orincorporated in or absorbed in or adsorbed on macro-, micro-, andnanoparticles, or macro-, micro-, and nanocapsules, for the treatment oftextiles, natural or synthetic fibres, wools, and any materials that maybe used for clothing or underwear for day or night intended to come intocontact with the skin, handkerchiefs or cloths, to exert their cosmeticeffect via this skin/textile contact and to permit continuous topicaldelivery.

IV. METHOD OF COSMETIC TREATMENT

The present invention also relates to a method of cosmetic treatment toimprove the general condition of the skin, comprising applying topicallyto the skin an effective amount of oridonin or a composition of oridoninand darutigenol or a combination of oridonin and darutoside, as definedabove, in particular:

-   -   to prevent and/or treat the signs of skin ageing;    -   to prevent and/or treat skin sagging, and/or improve the tone,        and/or firmness and/or elasticity of the skin;    -   to prevent and/or treat skin atrophy, and/or improve the density        of the dermis and epidermis;    -   to give or restore volume to the dermis and epidermis;    -   to prevent and/or treat skin dehydration;    -   to prevent and/or treat skin roughness;    -   to prevent and/or treat cellulite, to reduce the expansion        and/or prevent the development of adipose tissue in the        hypodermis;    -   to prevent and/or treat glycation of molecules in the skin;    -   to prevent and/or treat acne;    -   to prevent and/or treat skin breakdown due to the effects of        oxidation;    -   to prevent and/or treat inflammatory conditions.

The composition according to the invention can be applied locally ontoareas of the face, lips, neck, neckline, hands, feet or body. One of themajor advantages of the present invention is the possibility of beingable to perform whenever necessary or desirable, “gentle”, highlylocalised selective treatments using the topical non invasive method ofapplication.

In the case of an anti-wrinkle use for example, the application can beachieved in a very localized manner using a syringe or a microcannula.

It is however possible to consider a composition according to theinvention intended to be injected subcutaneously.

According to the invention, it is possible to propose severalcompartment devices or kits for implementing the process describedabove, which could include, for example, and without limitation, a firstcompartment containing a composition of oridonin and a secondcompartment containing a composition of another ingredient, darutigenolor darutoside for example, and/or excipients, the compositions containedin said first and second compartments being considered here as acomposition combination for a simultaneous, separate in time orsequential use in one of the treatments defined above.

According to other features, the method of treatment of the inventioncan be combined with one or more other methods of skin treatment, suchas light therapy, aromatherapy or heat treatments.

The invention also proposes a method in which the compound of theinvention is the active agent of cosmeceutical or nutraceuticalcomposition orally administered.

V. EXAMPLES

The following examples describe and demonstrate various aspects whithinthe scope of the present invention. The examples are given solely forpurposes of illustration and should not be construed as a limitation ofthe present invention. Also by way of illustration, several cosmeticformulations are listed. The formulations are representative of theinvention, but do not restrict it.

A—IN VITRO STUDIES

Darutoside used in the Studies is the darutoside molecule, commerciallyavailable under the trade name Darutigenol™.

The tested products are:

-   -   pure oridonin used at the following concentrations:        -   1.5 ppm, 3 ppm and 4.5 ppm;    -   pure darutoside used at the following concentrations:        -   5 ppm, 10 ppm and 15 ppm;    -   A combination of oridonin and darutoside and used at the        following concentrations:        -   1.5 ppm of oridonin and 5 ppm of darutoside;        -   3 ppm of oridonin and 10 ppm of darutoside;        -   4.5 ppm of oridonin and 15 ppm of darutoside.

1. Fighting Oxidative Stress

a. Reduction in Peroxyl Radicals: ORAC Test

The Oxygen-Radical Absorbance Capacity (ORAC) test is a method enablingevaluation of the antioxidant capability of molecules and extracts ofplant origin. A free radical generator (peroxyl radical) is placed incontact with a substrate revealing free radical presence: fluorescein.The free radical-induced dimerization of fluorescein decreases itsfluorescence. The antioxidant molecules will reduce this degradation

Results:

TABLE 1 Action of oridonin and of a combination of oridonin anddarutoside on the reduction of the destruction of fluorescein by freeradicals. (n = 6). Concentration of oridonin 1.5 ppm 3 ppm 4.5 ppmoridonin effect +14%; p < 0.01 +4%; dns −4%; dns Concentrations oforidonin 1.5 ppm of oridonin + 3 ppm of oridonin + 4.5 ppm of oridonin +and darutoside 5 ppm of darutoside 10 ppm of darutoside 15 ppm ofdarutoside Effect of oridonin and darutoside −15%; p < 0.01 −24%°; p <0.01 −33%; p < 0.01 dns = non significative difference/control

b. Evaluation of the Antioxidation Power of the Ordionin/DarutosideCombination: ROS on Human Dermal Fibroblasts (DCFH-DA Method)

Human dermal fibroblasts are placed in contact to theoridonin/darutoside combination during 24 h, then in contact with theDCFH-DA probe (2,7′-dichlorofluorescein diacetate). This probe, when ithas been metabolized in the cell, becomes sensitive to the redox statusof the cell. Cells are then exposed to oxidative stress with hydrogenperoxide.

After rinsing, the fluorescence is determined in order to compare theresidual oxidation level of the cells with oridonin and darutosidecombination compared to that of the negative control (after LEBEL et al,1992, modified).

Results:

TABLE 2 Effect of the ordinonin/darutoside combination on the reductionof intracellular oxidation. UFA/wells means Concentration of oridoninand darutoside respectively: (N = 7 tests/case) Control 1.5 ppm + 5 ppm3 ppm + 10 ppm 4.5 ppm + 15 ppm without H₂O₂ 9226 8397 8478 7998 400 μMH₂O₂ 16312 15376 14648 13652 (n = 7)

The decrease of intracellular oxidation is significant with p<0.05 atthe concentrations of oridonin and of darutoside of respectively (3ppm+10 ppm) and (4.5 ppm+15ppm).

c. Stimulation of Reduced Glutathione (GSH) Synthesis

Human keratinocytes at confluence are exposed 24 h to tested products.Intracellular GSH concentration was determined by ELISA.

TABLE 3 Effect of oridonin and of the combination of oridonin anddarutoside on stimulation of intracellular GSH synthesis (n = 6). GSHchange as % of Concentration control oridonin  3 ppm +41%; p < 0.01 4.5ppm  +79%; p < 0.01 darutoside 10 ppm +3%; dns 15 ppm +2%; dns oridoninand darutoside   3 ppm + 10 ppm +48%; p < 0.01 combination 4.5 ppm + 15ppm +90%; p < 0.01

2. Strengthening of the Chromophore Collagen

a. Induction of Collagen I Synthesis

The stimulation of collagen I synthesis was evaluated by image analysisof immunolabeled human dermal fibroblast layers following exposure tovarious concentrations of oridonin and darutoside.

Results:

TABLE 4 Change in the production of Collagène I with oridonin anddarutoside. Concentrations respectively of Collagen I oridonin anddarutoside AFU/10⁶ cell. % change; significance Control —  7.35 ± 2.91Reference oridonin and 1.5 ppm + 5 ppm  10.64 ± 5.30 +45%; p < 0.06darutoside   3 ppm + 10 ppm 17.14 ± 7.47 +133%; p < 0.01 4.5 ppm + 15ppm 19.87 ± 9.98 +170%; p < 0.01 AFU: arbitrary fluorescence unit (n =5); No toxic effect was observed after 19 days of exposure.

b. Retriggering of Collagen I and III Synthesis; Aged Skin Model

Reconstructed skin (Full Thickness Skin, Phenion) was experimentallyaged using a topical corticosteroid (betamethasone), which reducedcollagen synthesis by the fibroblasts and thus weakened the structure ofthe dermal fibers.

About 8 h after exposure, the combination oridonin (4.5 ppm) anddarutoside (15 ppm) was applied to the surface of the skin specimens(n=3) daily for 4 days. In parallel, oridonin and darutoside freeplacebo was applied to the control skin specimens.

The skin specimens were frozen and sectioned. The sections wereimmunolabeled to monitor collagen I and collagen III. An analysis of thevariations was conducted on the microscope images.

Results:

TABLE 5 Variation of collagen I and III production after 4 days oforidonin and darutoside application Coll. I % change % change Coll. III% change % change (AFU) Coll. I Coll. I (AFU) Coll. III Coll. IIINon-aged control 26.8 ± 7.3 Ref. 1 — 25.5 ± 5.2 Ref. 1 — Aged skin +placebo 20.4 ± 4.8 −21%; Ref. 2 17.2 ± 3.9 −33%; Ref. 2 p < 0.06 p <0.01 Aged skin + oridonin 26.3 ± 4.9 +2%; +29%; 22.4 ± 5.0 −12%; +31%;4.5 ppm and dns p < 0.05 dns p < 0.05 Darutigenol ™ 15 ppm AFU:arbitrary fluorescence unit

As expected, the results show that, for the experimentally aged skinspecimens, collagen I and III syntheses were markedly reduced (−21 and−33%, respectively) vs. the non-aged control specimen. The use oforidonin and darutoside combination enabled maintenance of a “normal”state since the collagen labeling was similar to that of the non-agedcontrol.

c. Reduction in MMP-1 Synthesis

Dermal human fibroblasts were exposed to the combinationoridonin+darutoside for 48 h. Following exposure, the MMP-1 present inthe culture medium was assayed by ELISA.

Results:

TABLE 6 Change in MMP-1 production in the presence of oridonin anddarutoside MMP-1 % change; Concentration (ng/10⁶ cells) significanceControl — 1156 +/− 100 Reference oridonin and   3 ppm + 10 ppm 956 +/−66 −17%; p < 0.05 darutoside 4.5 ppm + 15 ppm  658 +/− 112 −43%; p <0.01 (n = 3)

The results obtained on the chromophore, collagen, showed that acombination of oridonin and darutoside is endowed with the property ofintensifying collagen synthesis, including in experimentally aged skin,and limiting the degradation of the matrix by repressing MMP-1 formation(−43% with 4.5ppm of oridonin+15 ppm of darutoside).

3. Action on the Red Chromophore

a. Change in VEGF Synthesis

Cultured human keratinocytes were exposed to the products to be testedfor 24 h. The cells were then subjected to UVB irradiation in buffer andthen again exposed to the products for 24 h. After exposure, VEGF wasdetermined by ELISA.

Results:

TABLE 7 Change in VEGF production in the presence of the combination oforidonin and darutoside VEGF change in control %; Concentrationsignificance oridonin and darutoside 3 ppm + 10 ppm −47%; p < 0.01combination (n = 4)

b. Evaluation of the Anti-Redness Effect: Het-CAM Method

The Het-CAM model is recommended as an alternative method for theevaluation of the irritant effect of cosmetics. The model uses eggs at avery early stage of development since the nervous system is not yetfully developed (JORF No. 300, Dec. 26, 1996).

A moderately irritant product induces instantaneous changes in thecapillary density of the chorioallantoic membrane. Previously invisibleblood vessels become clearly visible under the effect of vasodilatation.This property was exploited to evaluate the effect of the combination oforidonin and darutoside.

The combination oridonin+darutoside was applied to the surface of thechorioallantoic membrane and, after incubation, a surfactant, used as anSDS irritant agent, in an appropriate concentration, was applied to thesurface of the membrane.

A score was determined by an experienced operator and compared to thatfor the membranes exposed to the irritant alone (negative control) andthat for the membranes exposed to aspirin, used as the positive control(JORF published method, modified).

Results:

TABLE 8 Change in inflammation index in the presence of 3% of thecombination of oridonin and darutoside Concentrations of oridonin anddarutoside Control respectively: 5000 ppm (Irritant alone) 4.5 ppm + 15ppm aspirin Mean score 10 +/− 1.63 4 +/− 2.12 2 +/− 2.06 Reference p <0.01 p < 0.01

The scores obtained showed that inflammation was very markedly slowed byaspirin and contained by the combination of oridonin and darutoside.

c. Change of the Inflammation

Cultured human fibroblasts were exposed to the products to be tested for24 h. Then the cells were UVB irradiated in a buffer and exposed againto the contact of the products for 24 h. After exposure, PGE2, IL6 andIL8 presence were evaluated by ELISA.

Results:

TABLE 9 Change in the PGE2, IL6 & IL8 production PGE2 change in IL6change in IL8 change in Concentration control % control % control %oridonin and 1.5 ppm + 5 ppm −46%; p < 0.01 −44%; p < 0.01 −48%; p <0.01 darutoside (n = 4)

4. Action on the Chromophore Melanin

i. Change in the Ability to Phagocyte Melanosomes

Cultured human keratinocytes were exposed to the combination of oridoninand darutoside for 48 h. Fluorescent melanosome models were then addedto the cells for phagocytosis. Intracellular fluorescence was thendetermined using a fluorescence reader (n=12).

Results:

TABLE 10 Change in keratinocyte melanosome phagocytosis in the presenceof 3% of the combination of oridonin and darutoside Phagocytosis %change; Concentrations (AFU/10⁴ cells) significance Control — 5996 +/−792 Reference oridonin and   3 ppm + 10 ppm 4640 +/− 875 −23%; p < 0.01darutoside 4.5 ppm + 15 ppm 3973 +/− 497 −34%; p < 0.01 AFU: Arbitraryfluorescence unit

The combination oridonin and darutoside thus reduced, in adose-dependent manner, the ability of keratinocytes to phagocytemelanosomes.

ii. Change in the Dendricity of Melanocytes

Human melanocytes were exposed to media conditioned with humankeratinocytes exposed to the combination of oridonin and darutoside for48 h. These media were recovered and putted for 48 h on a humanmelanocyte culture, then the layers were fixed and the cells observed.

Using an image analysis software, the number and length of the dentritewere determined (n=150 cells/case).

Results:

TABLE 11 Change in the melanocyte dendricity in presence of thecombination oridonin and darutoside Concentrations of oridonin 3 ppm andof Control darutoside 10 ppm Mean number of dendrite/cell   2.6 ± 0.9  2.5 ± 0.8 Mean length of dendrites 25.6 μm ± 14.4 17.2 μm ± 11.3 %Change; significance Reference −33%; p < 0.01

These results show that the average total number of dendrites is notsignificantly reduced by the combination oridonin and darutoside.

However the length of dendrites, and thus the ability of melanocytes totransfer their melanosomes, is reduced by 33% (p<0.01).

iii. Change in the Melanogenesis of Human Melanocytes in Monolayer

Human melanocytes were cultured and exposed with the test products for 5days. After incubation the melanin content was measured in cellhomogenates (n=4).

TABLE 12 % Change/control (melanin content). Concentrations of oridoninand oridonin and darutoside oridonin darutoside darutoside 125 ppm oforidonin + 3.75 −16%; p < 0.01 +1%; dns −25%; p < 0.01 ppm of darutoside5 ppm of oridonin + 5 −21%; p < 0.01 +2%; dns −26%; p < 0.01 ppm ofdarutoside 2.25 ppm of oridonin + 7.5 −23%; p < 0.01 −4%; dns −36%; p <0.01 ppm of darutoside 3 ppm of oridonin + 10 −34%; p < 0.01 −7%; p <0.05 −45%; p < 0.01 ppm of darutoside

5. Slimming

Human preadipocytes are cultured and induced to differentiate in thepresence of oridonin. After 10 days of differentiation, G3PDH activitywas measured in cell homogenates as a marker of differentiation. (n=4).

TABLE 13 Act G3PDH % Change; Concentrations (mU/10⁶ cell) significanceControl — 220.2 +/− 32.8 Reference oridonin 2.7 ppm 162.1 +/− 31.4 −26%;p < 0.05 3.6 ppm 127.7 +/− 19.2 −42%; p < 0.01

A dose-dependent and significant decrease of the activity of G3PDH ofhuman adipocytes in the presence of oridonin is observed compared to thenontreated case (control).

B—FORMULATION EXAMPLES

a) Comprising Oridonin

Pa is a solution comprising between 0.00001% and 50% of oridonin. Thepreparation P1 is an embodiment of the invention. The amount of suchpreparation in a cosmetic composition can vary in a large extend.

Example P1

Starting materials Wt % Water 20.0000 Butylen glycol 79.9320 oridonin*0.0180 *pure oridonin amount

Formulation n° 1: Anti-Wrinkle Day Cream

Starting materials CTFA name % % Phase A H₂O Qsp100 Qsp100 Ultrez 10Carbomer 0.10 0.10 Phase B P1 3.00 3.00 Phase C Dermaxyl ™ — 2.00 VolpoS 2 Steareth 2 0.60 0.60 Crodafos CES Cetearyl alcohol 4.00 4.00 dicetylphosphate & Ceteth-10 phosphate Crodamol STS PPG-3 Benzyl Ether 2.002.00 Myristate Crodamol OSU Dioctyl Succinate 7.00 7.00 Crill 3 SorbitanStearate 1.60 1.60 Nipagine Methyl Paraben 0.30 0.30 Phase D Potassiumsorbate Potassium Sorbate 0.10 0.10 Phase E NaOH 30% Sodium Hydroxide0.35 0.35 H₂O 3.50 3.50 Phase F Fragrance 0.10 0.10 Dermaxyl ™ is aproduct of Sederma (WO2004/101609): an anti-ageing agent comprising theassociation of ceramide 2, the stratum corneum cement and thepalmitoylated matrikine Pal-Val-Gly-Val-Ala-Pro-Gly. Dermaxyl ™stimulates cell communication and then repairs the age related skindamage. The presence of Dermaxyl ™ in the cream reinforces theanti-ageing properties of the oridonin ingredient of the presentinvention.

Operating Procedure:

Phase A: Powder Ultrez 10 in water. Leave for swelling 20 minutes. Thenweigh and heat phase B until dissolution. Add phase B in phase A. Weighphase C. Heat phase A+B and phase C at 80° C. under water-bath. Understirring, pour phase C into phase A+B. Homogenize, then add phase D.Homogenize, then add phase E around 50° C. Add phase F around 35° C.

Formulation n° 2: Anti-Ageing Tightener Gel

Starting materials CTFA name % Phase A Natrosol 250M Hydroxyethylcellulose 2.00 Jaguar HP 105 Guar gum 0.70 H₂O Qsp100 Sorbate depotassium Potassium Sorbate 0.10 Phase B Pure oridonin 0.05 NipagineMethyl paraben 0.20 Glycerin Glycerin 40.00 Phase C H₂O 8.00 Ultrez 10Carbomer 0.40 Phase D NaOH 30% Sodium hydroxide 0.40 H₂O 4.00 Phase ESkin tightener ST ™ 10.00 Phase F Crillet 1 Polysorbate 20 1.00Fragrance Parfume 0.10 Skin tightener ST ™ is a cosmetic ingredient ofSederma: it tightens and smoothes skin. It is an association ofprolamines (wheat proteins with a very high molecular weight, very richin glutamine/glutamic acid with polymannuronate (a hydrophilicpolysaccharide from algae Macrocystis pyrifera).

Operating Procedure:

Weigh phase A. Let swell under stirring propeller v=300 rpm for 2 hours.Weigh phase B and heat until dissolved. Add phase B into phase A undernormal stirring. Weigh phase C and let swell without stirring for ½hour. Add phase C into phase A+B, mix well. Mix phase D then add intophase A+B+C. Stir blade 300 rpm. Then add phase E, mix well. Weigh andmix phase F. Then add phase F in the previous phase, mix well.

Formulation n° 3: Anti-Wrinkle and Anti-Rednesses Lotion

Starting materials CTFA name % % Phase A H₂O Water Qsp100 Qsp100 Phase BVolpo G 26 Glycereth 26 4.00 4.00 Phenoxyethanol Phenoxytethanol 1.001.00 Pure oridonin 0.05 0.05 Phase C Crillet 1 Polysorbate 20 2.00 2.00Verbena Fragrance Fragrance 0.10 0.10 Phase D Phytotonine ™ — 5.00Phytotonine ™: is a cosmetic ingredient of Sederma: a concentratedhydroglycolic extract of Arnica, Cypress and Solomon's Seal.Phytotonine ™ reinforces vascular walls and improves microcirculation inveins and capillary vessels.

Operating Procedure:

Weigh phase A. Weigh phase B and heat until completely dissolved. Thenadd phase B into phase A, stir under propeller v=300 rpm. Weigh and mixphase C. Then add phase C into phase A+B, stir under propeller v=300rpm. Then add the phase D in phase A+B+C. Homogenize under propeller,v=300 rpm.

Formulation n° 4: Slimming Cream

Starting materials CTFA name % % Phase A Ultrez 10 Carbomer 0.40 0.40H₂O Qsp100 Qsp100 Phase B Pure Oridonin 0.05 0.05 Nipagine Methylparaben 0.20 0.20 Glycerin Glycerin 10.00 10.00 Phase C Natrosol 250MHydroxyethyl cellulose 0.20 0.20 Phase D Crillet 1 Polysorbate 20 2.002.00 Crodamol OP EthylHexyl Palmitate 4.00 4.00 DC 200 Dimethicone 3.003.00 Pemulen TR2 Acrylates/10-30 0.20 0.20 Alkyl Acrylates cross polymerPhase E Sorbate de potassium Potassium Sorbate 0.10 0.10 Phase F NaOH30% sodium hydroxide 0.60 0.60 H₂O 6.00 6.00 Phase G Ethanol 95 Ethanol3.00 3.00 Phase H Bodyfit ™ — 2.50 Phase I Fragrance Fragrance 0.10 0.10Bodyfit ™: is a product of Sederma (WO2004/024695): it diminishes theappearance of cellulite and enhances skin firmness. It contains glaucinein a water-soluble excipient. Glaucine is a multifunctional moleculethat stimulates lipolysis and inhibits the appearence of new adipocytes,by calcium flow regulation. Bodyfit ™ can reinforce the action of theslimming action of oridonin.

Operating Procedure:

Phase A: Sprinkle Ultrez 10 in water, let swell 30 minutes. Mix phase Band heat until dissolved. Add phase C into phase B and mix. Pour phaseB+C in phase A under stirring propeller v=300 rpm. Let rise 1 hour. Thenadd phase D, under stirring propeller v=300 rpm. Add phase Eextemporaneously, under stirring propeller v=300 rpm. Neutralize withphase F under stirring blade v=300 rpm. Add phase G, homogenize. Addphase H and then phase I, homogenize at the end. Chek pH +/−6.00.

b) Comprising Oridonin and Darutoside or Darutigenol

Pb is a solution comprising between 0.00001% and 50% and 0.00001% oforidonin and 0.00001% and 80% of darutoside (sold under the commercialname Darutigenol™).

Preparation P2 is an embodiment of the invention. The amount of such apreparation in a cosmetic composition can vary in a large extend.

Example P2

Ingredients Wt % Water 20.0000 Butylen glycol 79.9320 oridonin* 0.0180darutoside* 0.0500 *Amount of pure darutoside and oridonin.

Formulation n° 5: Anti-Wrinkle Day Cream

Starting materials CTFA name % % Phase A H₂O Qsp100 Qsp100 Ultrez 10Carbomer 0.10 0.10 Phase B Glycerin Glycerin 5.00 5.00 Phase CDermaxyl ™ — 2.00 Volpo S2 Steareth 2 0.60 0.60 Crodafos CES Cetearylalcohol dicetyl 4.00 4.00 phosphate & Ceteth- 10 phosphate Crodamol STSPPG-3 Benzyl Ether 2.00 2.00 Myristate Crodamol OSU Dioctyl Succinate7.00 7.00 Crill 3 Sorbitan Stearate 1.60 1.60 Nipagine Methyl Paraben0.30 0.30 Phase D Potassium Sorbate Potassium Sorbate 0.10 0.10 Phase ENaOH 30% Sodium Hydroxide 0.35 0.35 H₂O 3.50 3.50 Phase F P2 3.00 3.00Phase G Fragrance 0.10 0.10

Operating Procedure:

Phase A: Sprinkle Ultrez 10 in the water, let swallow 20 minutes. Weighphase B. Add phase B into phase A. Weigh phase C, heat phase A+phase Band phase C to 80° C. in a water bath. Under stirring staro v=30%, pourphase C into phase A+B, homogenize, then add phase D, homogenize. Thenadd at about 50° C. phase E. Add phase F around 35° C. Add phase G, mixwell.

Formulation n° 6: Anti-Rednesses Lotion

Starting materials CTFA name % Phase A H₂O Water Qsp100 Phase B Volpo G26 Glycereth 26 4.00 Phenoxyethanol Phenoxytethanol 1.00 Phase C Crillet1 Polysorbate 20 2.00 Verbena Fragrance Fragrance 0.10 Phase D P2 3.00Phase E Phytotonine ™ 5.00

Operating Procedure:

Weigh phase A. Weigh and mix phase B until complete solubilization. Thenadd phase B into phase A, stir under the propeller, v=300 rpm. Weigh andmix phase C. Add phase C into phase A+B, under propeller, v=300 rpm. Addphase D into phase A+B+C. Well homogenize, under propeller, v=300 rpm.Then add phase E in the previous phase. Well homogenize under propeller,v=300 rpm.

Formulation n° 7: Anti-Ageing Cream

Starting materials CTFA name % Phase A H₂O Water Qsp100 Ultrez 10Carbomer 0.25 Phase B Butylene glycol Butylene glycol 2.00Phenoxyethanol Phenoxytethanol qs Phase C Volpo S 2 Stereth-2 0.40 VolpoS 10 Stereth-10 1.20 Crodafos CES Cetearyl alcohol dicetyl 4.00phosphate & Ceteth-10 phosphate Crodacol CS90 Cetearyl Alcohol 0.50Laurocapram Azone 2.50 DC 345 Cyclohexasiloxane (and) 2.00Cyclopentasiloxane Crodamol OSU Diethylhexyl Succinate 7.00 Phase DPotassium sorbate Potassium Sorbate Phase E H₂O Water 3.00 NaOH 30%Sodium Hydroxide 0.40 Phase F P2 3.00 Phase G Oligoceane ™ Maris LimusExtract and 0.2 Ostrea Shell Extract and aqua and Propylene Glycol PhaseH Venuceane ™ Thermus Thermophillus 2.00 Ferment and Glycerin

Operating Procedure:

Weigh phase A and allow it to swell without stirring for 30 min Heatphase A at 75° C. in a water-bath. Weigh phase B and mix thoroughly. Addphase B into phase A at 75° C. in a water-bath. Weigh phase C and heatat 75° C. in a water-bath. Mix thoroughly. Pour phase C into phase A+Bunde Staro stirring, rate: 1000 rpm. Mix thoroughly. Freshly add phaseD. Add phase E, mix thoroughly. Adjust the pH to 6 with phase E at atemperature below 35° C. Add phase F, mix thoroughly. Add phase G, mixthoroughly. Then add phase H and mix thoroughly.

C—IN VIVO STUDIES

I In Vivo Test

Protocol

Study Inclusion Criteria:

Adult women of mean age 58 years having wrinkles and fine lines on theface or the neckline.

An initial joint panel of 12 subjects was used.

UV radiation and sun exposure sessions and tanning product applicationswere prohibited over the month preceding the study and during the study.The subjects were required to use only the cosmetics supplied throughoutthe duration of the study.

Study Type and Duration

The study was conducted using non-invasive methods, vs. a control site,each subject acting as its own control. The cream formulated with 3% ofP1 (Formulation n° 1 without the ingredient Dermaxyl™) and the controlcream were applied to opposite sides of the face; using massage, twicedaily for 2 months, at the eye corner.

Safety

The products were well tolerated by all the subjects.

Studied parameter: Average depth of the main wrinkle

Formulation n°1 Placebo Diminution of the depth Between −10 and −20% −5%between +5% of the main wrinkle

Significant difference between Formulation n° 1 and placebo is observed.

II In Vivo Studies with a Formulation Product Containing a Combinationof Oridonin and Darutoside

The Following Cream Products Were Used to Performe the Studies

Cream composition according to Placebo Starting materials CTFA name theinvention % cream % Phase A H₂O Water Qsp100 Qsp100 Ultrez 10 Carbomer0.25 0.25 Phase B Butylene glycol Butylene glycol 2.00 2.00Phenoxyethanol Phenoxytethanol qs qs Phase C Volpo S 2 Stereth-2 0.400.40 Volpo S 10 Stereth-10 1.20 1.20 Crodafos CES Cetearyl alcohol 4.004.00 dicetyl phosphate & Ceteth-10 phosphate Crodacol CS90 CetearylAlcohol 0.50 0.50 Laurocapram Azone 2.50 2.50 DC 345 Cyclohexasiloxane(and) 2.00 2.00 Cyclopentasiloxane Crodamol OSU Diethylhexyl Succinate7.00 7.00 Phase D Potassium sorbate Potassium Sorbate Phase E H₂O Water3.00 3.00 NaOH 30% Sodium Hydroxide 0.40 0.40 Phase F Excipient 3.00 —P2 — 3.00

Operating Procedure:

Weigh phase A and allow it to swell without stirring for 30 min. Heatphase A at 75° C. in a water-bath. Weigh phase B and mix thoroughly. Addphase B into phase A at 75° C. in a water-bath. Weigh phase C and heatat 75° C. in a water-bath. Mix thoroughly. Pour phase C into phase A+Bunde Staro stirring, rate: 1000 rpm. Mix thoroughly. Freshly add phaseD. Add phase E, mix thoroughly. Adjust the pH to 6 with phase E at atemperature below 35° C. Add phase F. Mix thoroughly.

Protocol of the Studies

Inclusion Criteria Specific to the Study

Adult women aged between 45 and 71 years (mean age: 58 years) with agespots (lengitines), hyperpigmented or red areas, fine lines and wrinkleson the face or neckline were selected. Subjects with two criteria in thesame area were priority included.

An initial joint panel of 26 subjects was used. Each subject wassubsequently classified as a function of chromophores. Since it wassometimes difficult to obtain, for all the subjects, the presence of thethree pertinent chromophores at the same site, an optimal panel (meetingthe screening criteria for each chromophore and site) of between 22 and25 subjects was used.

Hormonal consistency over the 3 months preceding the study and duringthe study was required. UV radiation and sun exposure sessions andtanning product application were prohibited over the month preceding thestudy and during the study. The subjects were required to use only thecosmetics supplied throughout the duration of the study.

Study Type and Duration

The study was conducted using non-invasive methods, vs. a control site,each subject acting as its own control. The cream formulated with 3% ofP2 (Foimulation n° 5) and the control cream were applied to oppositesides of the face and neckline, using massage, twice daily for 2 months.

Safety

The products were well tolerated by all the subjects.

1. Evaluation of the Chromophore Collagen by Echography and SIAscopy®

a. Echography

The density of the dermis, and hence the density the collagen itsprincipal component, can be determined by echography. Ultrasounds wereemitted on the skin zone of interest using an echographic probe. Theintensity of the sound waves reflected (or echoes) by the correspondingtissues is a function of tissue density. An analysis of the “slices”obtained enabled estimation of this variation in density.

Young skin is highly echogenic since it is denser than more elderlyskin, which has areas of heterogeneity (variable numbers of irregularnon-echogenic fields). The measurements given below, were recorded usinga Dermascan C echograph system (Cortex) and a probe operating at afrequency of 20 MHz.

TABLE 14 Change in dermal collagen density of the neckline (mean value;index; 25 subjects; n = 9 determinations) Formulation n^(o)5 Control T0T 1 m T 2 m T0 T 1 m T 2 m Mean 14.58 +/− 2.6 15.97 +/− 3.6 17.13 +/−3.9 13.98 +/− 2.6 14.21 +/− 2.3 15.57 +/− 3.8 % change vs. T0 9.6% 17.5%1.6% 4.2% significance p < 0.05 p < 0.01 dns dns Significance vs. p <0.05 p < 0.01 control

With the cream according to the invention, there was a marked increasein the most echogenic zones reflecting an increase in the density ofdermal fibers such as collagen. The increase, which was noteworthy andsignificant as of the first month of application, increased furtherafter 2 months, reaching 17.5% (p<0.01). In parallel, the control siteshowed little change.

b. SIAscope®

The SIAscope® (Spectrophotometric Intracutaneous Analysis,AstronClinica) is a portable scanner combining the advantages of acamera and spectroscope.

On contact with the skin, the system takes a photograph and analyzes(from 400 to 1000 nm) the manner in which the light is absorbed orre-emitted by the skin.)

It is thus possible to quantify the various chromophores and, inparticular, which renders the system unique for the time being, analyzethe heterogeneity of the distribution of the chromophore, collagen.

Using the SIAscope® system, it is possible to “see” to a depth of 2 mmunder the skin.

Due to the problem of noise at the margins of the images, the peripheralcrown was removed, in a standardized manner, using a SIAscan® analysissystem developed for that purpose.

Each point (350,000 pixels/image) of the image has an intensity (grayscale) different from the point next to it. The sum of the intensitiesyields a mean and standard deviation which express the heterogeneity ofcollagen distribution over the image. This heterogeneity was monitoredbetween two phases.

The results obtained were correlated with published results (MATTS etal., 2005) in order to express) the pre- vs. post-change in theheterogeneity of collagen distribution (equivalent to a standarddeviation) as a variation in age.

TABLE 15 Change in the heterogeneity of collagen distribution over theface (mean standard deviation of collagen distribution; 25 subjects; n =3 determinations) Cream according to the invention Control/placeboDifference in Difference in T0 T 2 m heterogeneity T0 T 2 mheterogeneity Mean standard deviation 2.51 2.46 −0.0515 2.475 2.475 # 0Mean real age 58 years — — Estimate of age change — 53.8 years −4.2years # 0 Significance vs. T0 p = 0.05 dns Significance vs. control p <0.05

2. Evaluation of the Red Chromophore Melanin, by VISIA®

The VISIA® System (Canfield) is a photographic chamber for the face thatenables imaging under visible and cross-polarized light. Standardizationof the images is ensured by a computer-aided repositioning system and bycomplete control of the photography conditions. From thepre-/post-images, it is possible to obtain:

-   -   the redness (or vascularization) index    -   the melanin age spots index

These index are correlated with the number and intensity of age spots orrednesses in the skin area studied. For these two indexes, the VISIA®uses the RBXtm technology (Red/Brown subsurface analysis; Demerli etcoll., 2007).

TABLE 16 Change in the vascularization index/redness of the face (meanvalue index; 24 subjects, n = 3 determinations) Formulation n^(o)5Control T0 T 1 m T 2 m T0 T 1 m T 2 m Mean 1.206 +/− 0.380 1.107 +/−0.322 1.076 +/− 0.438 1.218 +/− 1.093 1.113 +/− 0.393 1.085 +/− 0.411 %change vs. T0 −8.2% −10.8% 1.8% −0.8% Significance p < 0.05 p < 0.05 dnsdns Significance vs. p < 0.05 p < 0.05 control

With the formulation n° 5, after the first month of application animportant and significant improvement (p>0.05) of 8.2% of thevascularization index is observed.

The effect is improved after 2 months and reaches around 11% ofimprovement. Compared to the control, these improvements are very muchbetter and significant (p<0.05).

3. Evaluation of the Brown Chromophore Haemoglobin; VISTA®

As explained before (paragraphe 2), the VISTA® analyses the melanin spotindex.

In addition, through a database of manufacturer linking parameters ofthousands of women to their age, it is possible to estimate thetheoretical age of a skin (Lintner et al., 2007). This calculation isavailable, however, only to melanin spots.

TABLE 17 Change in the melanin chromophore melanin (melanin spots) onthe face (mean value index; 24 subjects, n = 3 determinations).Formulation n^(o)5 Control T0 T 1 m T 2 m T0 T 1 m T 2 m Mean 3.93 +/−1.34 3.76 +/− 1.18 3.63 +/− 1.19 3.80 +/− 1.30 3.83 +/− 1.34 3.71 +/−1.17 % change vs. T0 −4.3% −7.6% 0.8% −2.5% Significance p < 0.05 p <0.05 dns dns Theoretical age gain −2.7 years −4.8 years +0.5 years −1.4years vs. T0 Significance vs. p < 0.05 p < 0.05 control

After applying the formulation n° 5, from 1 month, a large andsignificant decrease of melanin spots is observed.

These decrease, in T 2 months, of almost 8%, which corresponds to a gainof approximately 5 years of age on this parameter.

Compared to the control that does not undergo little or no change, theeffect is significant at T 1 month and T 2 months (p<0.05).

The invention claimed is:
 1. A cosmetic composition comprising aneffective amount of oridonin and darutoside and a physiological medium.2. The composition according to claim 1 wherein the amount of oridoninranges from 0.00001% to 50% by weight of the composition.
 3. Thecomposition according to claim 1 wherein the amount of darutoside rangesfrom 0.00001% to 80% by weight of the composition.
 4. The compositionaccording to claim 1 wherein the ratio of oridonin to darutoside rangesfrom 1:1000 to 10:1.
 5. The composition according to claim 1 wherein theoridonin is extracted from Rhabdosia rubescens.
 6. The compositionaccording to claim 1 wherein the darutoside is extracted fromSiegesbeckia orientalis.
 7. A method of improving the general conditionof skin comprising topically applying an effective amount of thecomposition of claim 1 to a subject in need thereof.
 8. A method oftreating signs of cutaneous aging comprising topically applying aneffective amount of the composition of claim 1 to a subject in needthereof.
 9. The method of claim 8 wherein said treating signs ofcutaneous aging includes treating wrinkles, fine lines, visible and/ortactile skin discontinuities; loss of firmness, elasticity and tone ofcutaneous tissue.
 10. The method of claim 8 wherein said treating signsof cutaneous aging includes treating oxidative stress and free radicals.11. The method of claim 8 wherein said treating signs of cutaneous agingincludes treating deterioration of chromophore distribution byrebalancing the distribution of haemoglobin and collagen.
 12. The methodof claim 8 wherein said treating signs of cutaneous aging includestreating melanin spots.
 13. The method of claim 8 wherein said treatingsigns of cutaneous aging includes reducing cutaneous redness.
 14. Thecomposition according to claim 1 wherein the amount of oridonin rangesfrom 0.0001% to 10% by weight of the composition.
 15. The compositionaccording to claim 1 wherein the amount of oridonin ranges from 0.001%to 3% by weight of the composition.
 16. The composition according toclaim 1 wherein the amount of darutoside ranges from 0.001% to 50% byweight of the composition.
 17. The composition according to claim 1wherein the amount of darutoside ranges from 0.01% to 3% by weight ofthe composition.
 18. The composition according to claim 1 wherein theratio of oridonin to darutoside ranges from 1:1000 to 1:1.
 19. Thecomposition according to claim 1 wherein the ratio of oridonin todarutoside ranges from 1:100 to
 1. 20. The composition according toclaim 1 further comprising at least one agent selected from the groupconsisting of centella asiatica, asiaticoside and asiatic acid, cafein,thein, theobromin, forskolin, esculin, esculoside, ACE inhibitors,Val-Trp, Neuropeptide Y inhibitors, enkephaline, gingko biloba, yam,dioscorea extract, rutin, yerba mate extract, guarana extract,oligosaccharides, exopolysaccharides, alcohol, carnitin, Ivy extract,focus extract, algae extract, Peumus boldus extract, palmitoylcarnitine,carnosine, taurine, cyclic AMP, and elderberry extract.
 21. Thecomposition according to claim 1 further comprising at least oneadditional active agent selected from the group consisting ofanti-aging, whitening, moisturizing, slimming, revitalizing, anti-acne,anti-inflammatory and anti-hair loss agents.
 22. The compositionaccording to claim 21 wherein said anti-aging agent contains a thermusthermophiles ferment.
 23. The composition according to claim 21 whereinsaid revitalizing agent contains mineral salts extracted from marinesediments and oyster shells.
 24. The composition according to claim 1further comprising one or more ingredients selected from the groupconsisting of cleaning agents, hair conditioning agents, skinconditioning agents, hair styling agents, antidandruff agents, hairgrowth promoters, perfumes, sunscreen compounds, sunblock compounds,pigments, moisturizers, film formers, hair colors, make-up agents,detergents, pharmaceuticals, thickening agents, emulsifiers, humectants,emollients, antiseptic agents, deodorant actives, surfactants andpropellants.
 25. The composition according to claim 1 wherein saidcomposition is in the form of a solution, dispersion, emulsion, paste,or powder, individually or as a premix, or in vehicles individually oras a premix in vectors such as macro-, micro-, or nanocapsules, macro-,micro- or, nanospheres, liposomes, oleosomes or chylomicrons, macro-,micro-, or nanoparticles or macro-, micro or nanosponges, micro or nanoemulsions, or adsorbed on organic polymer powders, talcs, bentonites, orother inorganic or organic supports.
 26. The composition of claim 1further comprising at least one compound capable of stimulatingextracellular matrix.
 27. The composition of claim 26 wherein saidcompound is selected from the group consisting of vitamin A, retinoicretinoid acid, retinol, retinoic acid, retinyl proprionate retinolpalmitate, vitamin B3, niacinamide, nicotinate tocopherol, vitamin B5,vitamin B6, vitamin B12, vitamin C, ascorbic acid, ascorbyl acid,ascorbyl glucoside, ascorbyl tetrapalmitate, magnesium, sodium ascorbylphosphate, vitamins E, F, H, K, PP, amino acids, arginine, ornithine,hydroxyproline, hydroxyproline dipalmitate, palmitoylglycine, peptides,copper peptides, Carnosine, allantoine, farnesol, biotine, adenosine,lactic acid, glycolic acid, glucosamine, acetylglucosamine, madecassicacid, asiaticoside and asiatic acids, ellagic acid, salicylic acid,stigmasterol, sitosterol, campesterol, brassicasterol, teprenone,genistein, equol, hexamidine, panthenol, dimethylaminoethanol (DMAE),oils containing DHA/EPA, shea butter, and glycerin.
 28. The compositionof claim 27 wherein the peptide is selected from the group consisting ofthe peptide of SEQ ID NO:1, SEQ ID NO: 2, SEQ ID NO:3, SEQ ID NO:4, andSEQ ID NO:5.